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I have tried multiple different ways to get Ensemble's Variant Effect Predictor (VEP) to properly install on my mac, but I keep getting same error.

In /Users/username/ensembl-vep/htslib
make: Nothing to be done for `all'.
 - unpacking ./Bio/tmp/biodbhts.zip to ./Bio/tmp/
./Bio/tmp/Bio-DB-HTS-2.11 - moving files to ./biodbhts
 - making Bio::DB:HTS
clang-4.0: error: invalid version number in '-mmacosx-version-min=12.4'
Warning: ExtUtils::CBuilder not installed or no compiler detected
Proceeding with configuration, but compilation may fail during Build

Created MYMETA.yml and MYMETA.json
Creating new 'Build' script for 'Bio-DB-HTS' version '2.11'
Building Bio-DB-HTS
Error: no compiler detected to compile 'lib/Bio/DB/HTS.c'.  Aborting
ERROR: Shared Bio::DB:HTS library not found

--> When I check for the version of clang, I always get version 12, not sure where clang-4.0 is. I think error is specifically not correct path to current version of C++.

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    $\begingroup$ Do you have xcode utilities installed on your mac? What else have you tried? $\endgroup$
    – Ram RS
    Dec 15, 2022 at 20:45

2 Answers 2

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You can try and get Perl's ExUtils::Builder, described here correctly installed and working, for example

perl -MCPAN -e shell
force install Bundle::CPAN

You might want to use brew to make the build safe.

I don't do this stuff, I use OSX, I would install ensemble's VEP via conda

conda install -c bioconda ensembl-vep

You might want to (good idea) create a specific environment and obviously download Anaconda or miniconda.

conda create --name vep
conda activate vep

It will work, the output is below. I didn't proceed with the installation because of the shear amount of stuff downloaded into a given conda environment. There's everything in there but the kitchen sink, like there is mafft, t-coffee, clustalw, muscle and clustalo required in the download. I am honestly clueless because they are all alignment algorithms. Anyway I honestly wouldn't chase the MCPAN stuff, in this instance I definitely recommend conda. Finally, you honestly you don't want all this extra stuff on your hard drive when you've finished just delete the entire environment.

The final point I'd like to make is muscle5 (which is also in there) has recently significantly been modified making all other aligners obsolete on the runtime issue, but has to be run under the super5 mode.

## Package Plan ##

  environment location: /opt/anaconda3/envs/XXX # environment was edited  out

  added / updated specs:
    - ensembl-vep


The following packages will be downloaded:

    package                    |            build
    ---------------------------|-----------------
    argtable2-2.13             |    h1de35cc_1001         2.7 MB  conda-forge
    clustalo-1.2.4             |       h9722bc1_5         331 KB  bioconda
    clustalw-2.1               |       hcd10b59_7         326 KB  bioconda
    ensembl-vep-108.2          | pl5321h4a94de4_0         3.1 MB  bioconda
    expat-2.4.9                |       he9d5cce_0         127 KB
    htslib-1.14                |       hc38c3fb_0         2.0 MB  bioconda
    libdeflate-1.7             |       h9ed2024_5          52 KB
    libgfortran-5.0.0          |11_3_0_hecd8cb5_28         142 KB
    libgfortran5-11.3.0        |      h9dfd629_28         1.4 MB
    libzlib-1.2.12             |       hfd90126_3          65 KB  conda-forge
    mafft-7.508                |       ha5712d3_0         8.7 MB  bioconda
    muscle-5.1                 |       hb339e23_1         298 KB  bioconda
    mysql-connector-c-6.1.11   |       hccea1a4_1         1.2 MB
    paml-4.9                   |       hb4d813b_6         1.2 MB  bioconda
    perl-algorithm-diff-1.1903 | pl5321hdfd78af_3          36 KB  bioconda
    perl-base-2.23             | pl5321hdfd78af_2          12 KB  bioconda
    perl-bio-asn1-entrezgene-1.73| pl5321hdfd78af_3          24 KB  bioconda
    perl-bio-coordinate-1.007001| pl5321hdfd78af_3          36 KB  bioconda
    perl-bio-db-hts-3.01       | pl5321hc7384eb_4         116 KB  bioconda
    perl-bio-featureio-1.6.905 | pl5321hdfd78af_4          41 KB  bioconda
    perl-bio-samtools-1.43     | pl5321h1f540d2_3         161 KB  bioconda
    perl-bio-tools-phylo-paml-1.7.3| pl5321hdfd78af_3          58 KB  bioconda
    perl-bio-tools-run-alignment-clustalw-1.7.4| pl5321hdfd78af_3          25 KB  bioconda
    perl-bio-tools-run-alignment-tcoffee-1.7.4| pl5321hdfd78af_5          25 KB  bioconda
    perl-bioperl-1.7.8         |       hdfd78af_0           8 KB  bioconda
    perl-bioperl-core-1.7.8    | pl5321h527b516_0         1.8 MB  bioconda
    perl-bioperl-run-1.007003  | pl5321hdfd78af_0         340 KB  bioconda
    perl-business-isbn-3.007   | pl5321hdfd78af_0          18 KB  bioconda
    perl-business-isbn-data-20210112.006| pl5321hdfd78af_0          21 KB  bioconda
    perl-capture-tiny-0.48     | pl5321hdfd78af_2          19 KB  bioconda
    perl-class-data-inheritable-0.09| pl5321hdfd78af_0          10 KB  bioconda
    perl-constant-1.33         | pl5321hdfd78af_2          12 KB  bioconda
    perl-data-dumper-2.183     | pl5321ha5712d3_1          38 KB  bioconda
    perl-dbd-mysql-4.046       | pl5321hcd10b59_4          94 KB  bioconda
    perl-dbi-1.643             | pl5321ha5712d3_1         602 KB  bioconda
    perl-devel-stacktrace-2.04 | pl5321hdfd78af_1          17 KB  bioconda
    perl-digest-hmac-1.04      | pl5321hdfd78af_0          10 KB  bioconda
    perl-digest-md5-2.58       | pl5321ha5712d3_1          18 KB  bioconda
    perl-encode-locale-1.05    | pl5321hdfd78af_7          13 KB  bioconda
    perl-exception-class-1.45  | pl5321hdfd78af_0          21 KB  bioconda
    perl-file-listing-6.15     | pl5321hdfd78af_0          14 KB  bioconda
    perl-file-slurp-tiny-0.004 | pl5321hdfd78af_2          10 KB  bioconda
    perl-file-sort-1.01        | pl5321hdfd78af_3          20 KB  bioconda
    perl-file-spec-3.48_01     | pl5321hdfd78af_2           6 KB  bioconda
    perl-getopt-long-2.54      | pl5321hdfd78af_0          31 KB  bioconda
    perl-html-parser-3.80      | pl5321hb3ea9af_0          67 KB  bioconda
    perl-html-tagset-3.20      | pl5321hdfd78af_4          14 KB  bioconda
    perl-http-cookies-6.10     | pl5321hdfd78af_0          22 KB  bioconda
    perl-http-daemon-6.14      | pl5321hdfd78af_0          20 KB  bioconda
    perl-http-date-6.05        | pl5321hdfd78af_0          13 KB  bioconda
    perl-http-message-6.36     | pl5321hdfd78af_0          54 KB  bioconda
    perl-http-negotiate-6.01   | pl5321hdfd78af_4          14 KB  bioconda
    perl-io-html-1.004         | pl5321hdfd78af_0          16 KB  bioconda
    perl-io-socket-ssl-2.074   | pl5321hdfd78af_0         162 KB  bioconda
    perl-io-string-1.08        | pl5321hdfd78af_4          12 KB  bioconda
    perl-io-tty-1.16           | pl5321ha5712d3_1          30 KB  bioconda
    perl-ipc-run-20200505.0    | pl5321hdfd78af_0          76 KB  bioconda
    perl-libwww-perl-6.67      | pl5321hdfd78af_0          97 KB  bioconda
    perl-libxml-perl-0.08      | pl5321hdfd78af_3          40 KB  bioconda
    perl-lwp-mediatypes-6.04   | pl5321hdfd78af_1          24 KB  bioconda
    perl-mime-base64-3.16      | pl5321ha5712d3_2          16 KB  bioconda
    perl-net-http-6.22         | pl5321hdfd78af_0          21 KB  bioconda
    perl-net-ssleay-1.92       | pl5321h5d619eb_1         299 KB  bioconda
    perl-ntlm-1.09             | pl5321hdfd78af_5          16 KB  bioconda
    perl-perlio-gzip-0.20      | pl5321h1f540d2_3          16 KB  bioconda
    perl-sereal-4.019          | pl5321hdfd78af_0          11 KB  bioconda
    perl-sereal-decoder-4.025  | pl5321ha5712d3_1         156 KB  bioconda
    perl-sereal-encoder-4.025  | pl5321ha5712d3_1         365 KB  bioconda
    perl-set-intervaltree-0.12 | pl5321h9722bc1_2          31 KB  bioconda
    perl-socket-2.027          | pl5321ha5712d3_3          29 KB  bioconda
    perl-sub-uplevel-0.2800    | pl5321ha5712d3_4          14 KB  bioconda
    perl-test-deep-1.130       | pl5321hdfd78af_0          37 KB  bioconda
    perl-test-differences-0.69 | pl5321hdfd78af_0          19 KB  bioconda
    perl-test-exception-0.43   | pl5321hdfd78af_3          15 KB  bioconda
    perl-test-harness-3.44     | pl5321hdfd78af_0          85 KB  bioconda
    perl-test-most-0.38        | pl5321hdfd78af_0          20 KB  bioconda
    perl-test-warn-0.36        | pl5321hdfd78af_2          14 KB  bioconda
    perl-text-csv-2.01         | pl5321hdfd78af_0          70 KB  bioconda
    perl-text-diff-1.45        | pl5321hdfd78af_1          23 KB  bioconda
    perl-time-local-1.30       | pl5321hdfd78af_0          12 KB  bioconda
    perl-timedate-2.33         | pl5321hdfd78af_2          31 KB  bioconda
    perl-tree-dag_node-1.32    | pl5321hdfd78af_0          43 KB  bioconda
    perl-try-tiny-0.31         | pl5321hdfd78af_1          19 KB  bioconda
    perl-uri-5.12              | pl5321hdfd78af_0          59 KB  bioconda
    perl-url-encode-0.03       | pl5321h527b516_0          12 KB  bioconda
    perl-www-robotrules-6.02   | pl5321hdfd78af_4          14 KB  bioconda
    perl-xml-dom-1.46          | pl5321hdfd78af_1          59 KB  bioconda
    perl-xml-dom-xpath-0.14    | pl5321hdfd78af_2          12 KB  bioconda
    perl-xml-parser-2.44       | pl5321h50c80e2_8         162 KB  bioconda
    perl-xml-regexp-0.04       | pl5321hdfd78af_3          10 KB  bioconda
    perl-xml-xpathengine-0.14  | pl5321hdfd78af_3          28 KB  bioconda
    t-coffee-11.00.8cbe486     |       h26a2512_0         1.1 MB  bioconda
    unzip-6.0                  |       h3b3adb9_0          71 KB
    ------------------------------------------------------------
                                           Total:        28.7 MB

The following NEW packages will be INSTALLED:

  argtable2          conda-forge/osx-64::argtable2-2.13-h1de35cc_1001
  blast              bioconda/osx-64::blast-2.12.0-h0370960_3
  clustalo           bioconda/osx-64::clustalo-1.2.4-h9722bc1_5
  clustalw           bioconda/osx-64::clustalw-2.1-hcd10b59_7
  ensembl-vep        bioconda/noarch::ensembl-vep-108.2-pl5321h4a94de4_0
  entrez-direct      bioconda/osx-64::entrez-direct-16.2-h193322a_1
  expat              pkgs/main/osx-64::expat-2.4.9-he9d5cce_0
  htslib             bioconda/osx-64::htslib-1.14-hc38c3fb_0
  libdeflate         pkgs/main/osx-64::libdeflate-1.7-h9ed2024_5
  libgfortran        pkgs/main/osx-64::libgfortran-5.0.0-11_3_0_hecd8cb5_28
  libgfortran5       pkgs/main/osx-64::libgfortran5-11.3.0-h9dfd629_28
  libidn2            pkgs/main/osx-64::libidn2-2.3.2-h9ed2024_0
  libunistring       pkgs/main/osx-64::libunistring-0.9.10-h9ed2024_0
  libzlib            conda-forge/osx-64::libzlib-1.2.12-hfd90126_3
  llvm-openmp        pkgs/main/osx-64::llvm-openmp-14.0.6-h0dcd299_0
  mafft              bioconda/osx-64::mafft-7.508-ha5712d3_0
  muscle             bioconda/osx-64::muscle-5.1-hb339e23_1
  mysql-connector-c  pkgs/main/osx-64::mysql-connector-c-6.1.11-hccea1a4_1
  paml               bioconda/osx-64::paml-4.9-hb4d813b_6
  pcre               pkgs/main/osx-64::pcre-8.45-h23ab428_0
  perl               pkgs/main/osx-64::perl-5.32.1-0_h435f0c2_perl5
  perl-algorithm-di~ bioconda/noarch::perl-algorithm-diff-1.1903-pl5321hdfd78af_3
  perl-archive-tar   bioconda/noarch::perl-archive-tar-2.40-pl5321hdfd78af_0
  perl-base          bioconda/noarch::perl-base-2.23-pl5321hdfd78af_2
  perl-bio-asn1-ent~ bioconda/noarch::perl-bio-asn1-entrezgene-1.73-pl5321hdfd78af_3
  perl-bio-coordina~ bioconda/noarch::perl-bio-coordinate-1.007001-pl5321hdfd78af_3
  perl-bio-db-hts    bioconda/osx-64::perl-bio-db-hts-3.01-pl5321hc7384eb_4
  perl-bio-featureio bioconda/noarch::perl-bio-featureio-1.6.905-pl5321hdfd78af_4
  perl-bio-samtools  bioconda/osx-64::perl-bio-samtools-1.43-pl5321h1f540d2_3
  perl-bio-tools-ph~ bioconda/noarch::perl-bio-tools-phylo-paml-1.7.3-pl5321hdfd78af_3
  perl-bio-tools-ru~ bioconda/noarch::perl-bio-tools-run-alignment-clustalw-1.7.4-pl5321hdfd78af_3
  perl-bio-tools-ru~ bioconda/noarch::perl-bio-tools-run-alignment-tcoffee-1.7.4-pl5321hdfd78af_5
  perl-bioperl       bioconda/noarch::perl-bioperl-1.7.8-hdfd78af_0
  perl-bioperl-core  bioconda/osx-64::perl-bioperl-core-1.7.8-pl5321h527b516_0
  perl-bioperl-run   bioconda/noarch::perl-bioperl-run-1.007003-pl5321hdfd78af_0
  perl-business-isbn bioconda/noarch::perl-business-isbn-3.007-pl5321hdfd78af_0
  perl-business-isb~ bioconda/noarch::perl-business-isbn-data-20210112.006-pl5321hdfd78af_0
  perl-capture-tiny  bioconda/noarch::perl-capture-tiny-0.48-pl5321hdfd78af_2
  perl-carp          bioconda/noarch::perl-carp-1.38-pl5321hdfd78af_4
  perl-class-data-i~ bioconda/noarch::perl-class-data-inheritable-0.09-pl5321hdfd78af_0
  perl-common-sense  bioconda/noarch::perl-common-sense-3.75-pl5321hdfd78af_0
  perl-compress-raw~ bioconda/osx-64::perl-compress-raw-bzip2-2.201-pl5321h9722bc1_0
  perl-compress-raw~ bioconda/osx-64::perl-compress-raw-zlib-2.105-pl5321h9722bc1_0
  perl-constant      bioconda/noarch::perl-constant-1.33-pl5321hdfd78af_2
  perl-data-dumper   bioconda/osx-64::perl-data-dumper-2.183-pl5321ha5712d3_1
  perl-dbd-mysql     bioconda/osx-64::perl-dbd-mysql-4.046-pl5321hcd10b59_4
  perl-dbi           bioconda/osx-64::perl-dbi-1.643-pl5321ha5712d3_1
  perl-devel-stackt~ bioconda/noarch::perl-devel-stacktrace-2.04-pl5321hdfd78af_1
  perl-digest-hmac   bioconda/noarch::perl-digest-hmac-1.04-pl5321hdfd78af_0
  perl-digest-md5    bioconda/osx-64::perl-digest-md5-2.58-pl5321ha5712d3_1
  perl-encode        bioconda/osx-64::perl-encode-3.19-pl5321ha5712d3_1
  perl-encode-locale bioconda/noarch::perl-encode-locale-1.05-pl5321hdfd78af_7
  perl-exception-cl~ bioconda/noarch::perl-exception-class-1.45-pl5321hdfd78af_0
  perl-exporter      bioconda/noarch::perl-exporter-5.72-pl5321hdfd78af_2
  perl-exporter-tiny bioconda/noarch::perl-exporter-tiny-1.002002-pl5321hdfd78af_0
  perl-extutils-mak~ conda-forge/noarch::perl-extutils-makemaker-7.64-pl5321hd8ed1ab_0
  perl-file-listing  bioconda/noarch::perl-file-listing-6.15-pl5321hdfd78af_0
  perl-file-slurp-t~ bioconda/noarch::perl-file-slurp-tiny-0.004-pl5321hdfd78af_2
  perl-file-sort     bioconda/noarch::perl-file-sort-1.01-pl5321hdfd78af_3
  perl-file-spec     bioconda/noarch::perl-file-spec-3.48_01-pl5321hdfd78af_2
  perl-getopt-long   bioconda/noarch::perl-getopt-long-2.54-pl5321hdfd78af_0
  perl-html-parser   bioconda/osx-64::perl-html-parser-3.80-pl5321hb3ea9af_0
  perl-html-tagset   bioconda/noarch::perl-html-tagset-3.20-pl5321hdfd78af_4
  perl-http-cookies  bioconda/noarch::perl-http-cookies-6.10-pl5321hdfd78af_0
  perl-http-daemon   bioconda/noarch::perl-http-daemon-6.14-pl5321hdfd78af_0
  perl-http-date     bioconda/noarch::perl-http-date-6.05-pl5321hdfd78af_0
  perl-http-message  bioconda/noarch::perl-http-message-6.36-pl5321hdfd78af_0
  perl-http-negotia~ bioconda/noarch::perl-http-negotiate-6.01-pl5321hdfd78af_4
  perl-io-compress   bioconda/osx-64::perl-io-compress-2.201-pl5321h9722bc1_0
  perl-io-html       bioconda/noarch::perl-io-html-1.004-pl5321hdfd78af_0
  perl-io-socket-ssl bioconda/noarch::perl-io-socket-ssl-2.074-pl5321hdfd78af_0
  perl-io-string     bioconda/noarch::perl-io-string-1.08-pl5321hdfd78af_4
  perl-io-tty        bioconda/osx-64::perl-io-tty-1.16-pl5321ha5712d3_1
  perl-io-zlib       bioconda/noarch::perl-io-zlib-1.11-pl5321hdfd78af_0
  perl-ipc-run       bioconda/noarch::perl-ipc-run-20200505.0-pl5321hdfd78af_0
  perl-json          bioconda/noarch::perl-json-4.10-pl5321hdfd78af_0
  perl-json-xs       bioconda/osx-64::perl-json-xs-2.34-pl5321hcd10b59_5
  perl-libwww-perl   bioconda/noarch::perl-libwww-perl-6.67-pl5321hdfd78af_0
  perl-libxml-perl   bioconda/noarch::perl-libxml-perl-0.08-pl5321hdfd78af_3
  perl-list-moreuti~ bioconda/noarch::perl-list-moreutils-0.430-pl5321hdfd78af_0
  perl-list-moreuti~ bioconda/osx-64::perl-list-moreutils-xs-0.430-pl5321ha5712d3_1
  perl-lwp-mediatyp~ bioconda/noarch::perl-lwp-mediatypes-6.04-pl5321hdfd78af_1
  perl-mime-base64   bioconda/osx-64::perl-mime-base64-3.16-pl5321ha5712d3_2
  perl-net-http      bioconda/noarch::perl-net-http-6.22-pl5321hdfd78af_0
  perl-net-ssleay    bioconda/osx-64::perl-net-ssleay-1.92-pl5321h5d619eb_1
  perl-ntlm          bioconda/noarch::perl-ntlm-1.09-pl5321hdfd78af_5
  perl-parent        bioconda/noarch::perl-parent-0.236-pl5321hdfd78af_2
  perl-pathtools     bioconda/osx-64::perl-pathtools-3.75-pl5321ha5712d3_3
  perl-perlio-gzip   bioconda/osx-64::perl-perlio-gzip-0.20-pl5321h1f540d2_3
  perl-scalar-list-~ bioconda/osx-64::perl-scalar-list-utils-1.62-pl5321ha5712d3_0
  perl-sereal        bioconda/noarch::perl-sereal-4.019-pl5321hdfd78af_0
  perl-sereal-decod~ bioconda/osx-64::perl-sereal-decoder-4.025-pl5321ha5712d3_1
  perl-sereal-encod~ bioconda/osx-64::perl-sereal-encoder-4.025-pl5321ha5712d3_1
  perl-set-interval~ bioconda/osx-64::perl-set-intervaltree-0.12-pl5321h9722bc1_2
  perl-socket        bioconda/osx-64::perl-socket-2.027-pl5321ha5712d3_3
  perl-sub-uplevel   bioconda/osx-64::perl-sub-uplevel-0.2800-pl5321ha5712d3_4
  perl-test-deep     bioconda/noarch::perl-test-deep-1.130-pl5321hdfd78af_0
  perl-test-differe~ bioconda/noarch::perl-test-differences-0.69-pl5321hdfd78af_0
  perl-test-excepti~ bioconda/noarch::perl-test-exception-0.43-pl5321hdfd78af_3
  perl-test-harness  bioconda/noarch::perl-test-harness-3.44-pl5321hdfd78af_0
  perl-test-most     bioconda/noarch::perl-test-most-0.38-pl5321hdfd78af_0
  perl-test-warn     bioconda/noarch::perl-test-warn-0.36-pl5321hdfd78af_2
  perl-text-csv      bioconda/noarch::perl-text-csv-2.01-pl5321hdfd78af_0
  perl-text-diff     bioconda/noarch::perl-text-diff-1.45-pl5321hdfd78af_1
  perl-time-local    bioconda/noarch::perl-time-local-1.30-pl5321hdfd78af_0
  perl-timedate      bioconda/noarch::perl-timedate-2.33-pl5321hdfd78af_2
  perl-tree-dag_node bioconda/noarch::perl-tree-dag_node-1.32-pl5321hdfd78af_0
  perl-try-tiny      bioconda/noarch::perl-try-tiny-0.31-pl5321hdfd78af_1
  perl-types-serial~ bioconda/noarch::perl-types-serialiser-1.01-pl5321hdfd78af_0
  perl-uri           bioconda/noarch::perl-uri-5.12-pl5321hdfd78af_0
  perl-url-encode    bioconda/osx-64::perl-url-encode-0.03-pl5321h527b516_0
  perl-www-robotrul~ bioconda/noarch::perl-www-robotrules-6.02-pl5321hdfd78af_4
  perl-xml-dom       bioconda/noarch::perl-xml-dom-1.46-pl5321hdfd78af_1
  perl-xml-dom-xpath bioconda/noarch::perl-xml-dom-xpath-0.14-pl5321hdfd78af_2
  perl-xml-parser    bioconda/osx-64::perl-xml-parser-2.44-pl5321h50c80e2_8
  perl-xml-regexp    bioconda/noarch::perl-xml-regexp-0.04-pl5321hdfd78af_3
  perl-xml-xpatheng~ bioconda/noarch::perl-xml-xpathengine-0.14-pl5321hdfd78af_3
  t-coffee           bioconda/osx-64::t-coffee-11.00.8cbe486-h26a2512_0
  unzip              pkgs/main/osx-64::unzip-6.0-h3b3adb9_0
  wget               pkgs/main/osx-64::wget-1.21.3-h6dfd666_0
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VEP requires gcc and g++ for installation1. Before running the build script, try setting the CC and CXX environment variables to the paths of your gcc and g++ compilers, respectively:

export CC=gcc
export CXX=g++

You'll need to install these compilers if they don't already exist on your system.

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