GnomXMiss: Missense Variant Annotations Derived From AlphaMissense Enriched With gnomAD, VEP, and ClinVar

GnomXMiss per-protein files

<uniprot_id>_GnomXMiss.tsv

Each file contains available missense variants for a UniProt canonical protein present in the AlphaMissense data dump that could be crossed referenced with:

gnomAD allele frequencies (overall + subpopulation-specific)

AlphaMissense pathogenicity scores

VEP annotations (GENCODE v46)

ClinVar variant metadata

Only proteins for which all required annotations were successfully retrieved are included.

These files are sorted by residue_number and contain variants from the AlphaMissense hg38 missense dump together with variants in the matching genomic intervals of gnomad.joint.v4.1.sites.ht; we outer-merge both sources on (#CHROM, POS, REF, ALT) and annotate variants that lack information where possible.

Column descriptions

Below is the full set of columns that appear across the *_GnomXMiss.tsv files

Primary identifiers

uniprot_id

Canonical UniProtKB accession for the protein associated with the variant.

#CHROM

Chromosome name (e.g., chr1, chr2, chrX, chrY) based on GRCh38.

POS

1-based genomic coordinate of the variant (GRCh38).

REF, ALT

Reference and alternate nucleotides from gnomAD.

Protein-level variant information

protein_variant

Amino-acid substitution in the format <RefAA><Protein_Sequence_Position><AltAA>, e.g. V600E.

residue_number

Integer position of the substitution extracted from protein_variant.

AlphaMissense annotation

am_class

Classification of variant pathogenicity:

likely_benign

ambiguous

likely_pathogenic

am_pathogenicity

Calibrated AlphaMissense pathogenicity score (0–1).

ClinVar annotations (if available)

existing_variation

ClinVar or dbSNP IDs extracted via Ensembl VEP.

clinvar_significance

e.g., Benign, Likely_pathogenic, VUS, etc.

clinvar_condition

Name(s) of associated disease conditions.

clinvar_disease_id

Disease database identifiers (MEDGEN, MONDO, OMIM, etc.).

clinvar_variant_id

ClinVar Variation ID.

gnomAD allele frequency data (v4) (if available)

These fields are derived from the joint gnomAD v4 release and represent population-level statistics (no individual data).

Overall

allele_count

allele_number

allele_frequency

homozygote_count

Population-specific allele frequencies

The dataset includes AF values for multiple ancestry groups:

nfe_allele_frequency — Non-Finnish European

fin_allele_frequency — Finnish

afr_allele_frequency — African/African American

eas_allele_frequency — East Asian

sas_allele_frequency — South Asian

amr_allele_frequency — Latino/Admixed American

ami_allele_frequency — Amish

asj_allele_frequency — Ashkenazi Jewish

mid_allele_frequency — Middle Eastern

remaining_allele_frequency — Remaining ancestry group

Sex-specific allele frequencies

XX_allele_frequency

XY_allele_frequency

(Some fields be empty depending on variant representation in gnomAD.)