Is BAP1 p.Ala316Val (c.947C>T) pathogenic?

BAP1 p.Ala316Val (c.947C>T) is classified Conflicting classifications of pathogenicity in BAP1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.0683); Very rare (popmax 0.00834%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with BAP1 p.Ala316Val (c.947C>T)?

BAP1 p.Ala316Val (c.947C>T) is associated with hereditary neoplastic syndrome, BAP1-related tumor predisposition syndrome (ClinVar).

How common is BAP1 p.Ala316Val (c.947C>T) in the general population?

BAP1 p.Ala316Val (c.947C>T) is very rare (popmax 0.00834%, amr) (gnomAD).

What do computational predictors say about BAP1 p.Ala316Val (c.947C>T)?

AlphaMissense predicts likely benign (score 0.0683) — an in-silico prediction, not a clinical call.

BAP1 p.Ala316Val

c.947C>T · rs1365625070 · VCV628708

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0683 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00834%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0683	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -6.92	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.29 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.4	GERP -3.8, phastCons 0.7
Overall
CADD	2.261	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00834% Admixed American · 5/59,984 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.000496% 8/1,613,548 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00834%	11,997
African / African-American	0.00134%	74,862
European (non-Finnish)	0.000169%	590,005

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.Ala316Val
Coding: c.947C>T
MANE Select: NM_007212 · reported on NM_004656
dbSNP: rs1365625070
Type: single nucleotide variant
Location: chr3:52405279 (GRCh38)
Structure: AlphaFold pLDDT 78.27 · 28 PDB
Residue 316: an α-helix

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: BAP1-related tumor predisposition syndrome

Similar variants

BAP1 p.Ala316= Benign/Likely benign ★★ same residue
BAP1 p.Ala316Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
BAP1 p.Ala316fs Pathogenic ★ 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-ala316val (accessed [today's date]).

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