Is BAP1 p.Ala167= (c.501G>A) pathogenic?

BAP1 p.Ala167= (c.501G>A) is classified Benign/Likely benign in BAP1 (ClinVar, Multiple submitters, 16 submitters; last evaluated 2026-06-01). Rare (popmax 0.495%, mid); Associated with melanoma, uveal, susceptibility to, 2.

What condition is associated with BAP1 p.Ala167= (c.501G>A)?

BAP1 p.Ala167= (c.501G>A) is associated with melanoma, uveal, susceptibility to, 2, BAP1-related tumor predisposition syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BAP1 p.Ala167= (c.501G>A) in the general population?

BAP1 p.Ala167= (c.501G>A) is rare (popmax 0.495%, mid) (gnomAD).

BAP1 p.Ala167=

c.501G>A · rs148631953 · VCV240060

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 16 submitters

gnomAD v4.1

Rare

rare (popmax 0.495%, mid)

Conditions

melanoma, uveal, susceptibility to, 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.8	GERP -3.8
Overall
CADD	4.227	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.495% Middle Eastern · 30/6,062 alleles

Filtering AF 0.356% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.309%

Overall 0.051% 824/1,614,180 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.495%	202
Ashkenazi Jewishnot grpmax-eligible	0.382%	262
Remaining individualsnot grpmax-eligible	0.104%	962
African / African-American	0.0546%	1,830
South Asian	0.0538%	1,859
Admixed American	0.0433%	2,308
European (non-Finnish)	0.0423%	2,365
Finnishnot grpmax-eligible	0.00156%	64,036

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: BAP1
Protein: p.Ala167=
Coding: c.501G>A
MANE Select: NM_004656
dbSNP: rs148631953
Type: single nucleotide variant
Location: chr3:52407253 (GRCh38)
Gene constraint: LOEUF 0.324 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.87 · 4 PDB
Residue 167: the uch catalytic domain; a β-strand

Full BAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

melanoma, uveal, susceptibility to, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: BAP1-related tumor predisposition syndrome hereditary neoplastic syndrome

Similar variants

BAP1 p.Ala167Val Uncertain significance ★★ ⚠ same residue
BAP1 p.Ala167Glu Uncertain significance ★ ⚠ same residue
BAP1 p.Ala167Thr Uncertain significance ★ ⚠ same residue
BAP1 c.1117-1G>A Likely pathogenic ★★ same condition
BAP1 c.122+1G>A Pathogenic ★★ same condition
BAP1 c.122+1G>T Pathogenic/Likely pathogenic ★★ same condition
BAP1 c.122+5G>A Pathogenic/Likely pathogenic ★★ same condition
BAP1 c.122+5G>C Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/bap1-p-ala167 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown