Is BAP1 p.Val476Ala (c.1427T>C) pathogenic?

BAP1 p.Val476Ala (c.1427T>C) is classified Benign/Likely benign in BAP1 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-30). AlphaMissense: likely benign (0.1018); Rare (popmax 0.109%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with BAP1 p.Val476Ala (c.1427T>C)?

BAP1 p.Val476Ala (c.1427T>C) is associated with hereditary neoplastic syndrome, BAP1-related tumor predisposition syndrome (ClinVar).

How common is BAP1 p.Val476Ala (c.1427T>C) in the general population?

BAP1 p.Val476Ala (c.1427T>C) is rare (popmax 0.109%, afr) (gnomAD).

What do computational predictors say about BAP1 p.Val476Ala (c.1427T>C)?

AlphaMissense predicts likely benign (score 0.1018) — an in-silico prediction, not a clinical call.

BAP1 p.Val476Ala

c.1427T>C · rs144060813 · VCV240048

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.1018 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.109%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.1018	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -5.69	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Overall
CADD	21.5	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 0.109% African / African-American · 82/74,904 alleles

Filtering AF 0.0904% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0833%

Overall 0.00551% 89/1,613,916 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.109%	913
Remaining individualsnot grpmax-eligible	0.0064%	15,621
Admixed American	0.005%	20,001

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.Val476Ala
Coding: c.1427T>C
MANE Select: NM_007212 · reported on NM_004656
dbSNP: rs144060813
Type: single nucleotide variant
Location: chr3:52403718 (GRCh38)
Structure: AlphaFold pLDDT 78.27 · 28 PDB

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.Val476Met 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
BAP1 c.1251-1G>A Likely pathogenic ★★ same condition
BAP1 c.1251-1G>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-val476ala (accessed [today's date]).

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