Is BAP1 p.Val162Ala (c.485T>C) pathogenic?

BAP1 p.Val162Ala (c.485T>C) is classified Uncertain significance in BAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-23). AlphaMissense: ambiguous (0.5418); Very rare (popmax 0.000254%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with BAP1 p.Val162Ala (c.485T>C)?

BAP1 p.Val162Ala (c.485T>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is BAP1 p.Val162Ala (c.485T>C) in the general population?

BAP1 p.Val162Ala (c.485T>C) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about BAP1 p.Val162Ala (c.485T>C)?

AlphaMissense predicts ambiguous (score 0.5418) — an in-silico prediction, not a clinical call.

BAP1 p.Val162Ala

c.485T>C · rs2153227845 · VCV3224470

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5418 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.5418	ambiguous
REVEL	0.256	benign-leaning
SaProt	LLR -5.40	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Overall
CADD	25.0	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 0.000254% European (non-Finnish) · 3/1,180,038 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,614,200 alleles · very rare exomes 3/1,461,886 · genomes 0/152,314 · joint denominator

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.Val162Ala
Coding: c.485T>C
MANE Select: NM_004656
dbSNP: rs2153227845
Type: single nucleotide variant
Location: chr3:52407269 (GRCh38)
Gene constraint: LOEUF 0.324 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.87 · 4 PDB
Residue 162: the uch catalytic domain

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

Similar variants

BAP1 p.Val162Leu Uncertain significance ★ same residue
BAP1 p.Val162Met Uncertain significance ★ same residue
BAP1 p.Val162= Likely benign ★ 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.1251-1G>A Likely pathogenic ★★ same condition
BAP1 c.1251-2A>G 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-val162ala (accessed [today's date]).

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