Is BAP1 p.Val386Ile (c.1156G>A) pathogenic?

BAP1 p.Val386Ile (c.1156G>A) is classified Conflicting classifications of pathogenicity in BAP1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-04-23). AlphaMissense: likely benign (0.0725); Very rare (popmax 0.00267%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with BAP1 p.Val386Ile (c.1156G>A)?

BAP1 p.Val386Ile (c.1156G>A) is associated with hereditary neoplastic syndrome, BAP1-related tumor predisposition syndrome (ClinVar).

How common is BAP1 p.Val386Ile (c.1156G>A) in the general population?

BAP1 p.Val386Ile (c.1156G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about BAP1 p.Val386Ile (c.1156G>A)?

AlphaMissense predicts likely benign (score 0.0725) — an in-silico prediction, not a clinical call.

BAP1 p.Val386Ile

c.1156G>A · rs372213315 · VCV579323

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0725 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0725	likely benign
REVEL	0.148	moderately benign-leaning
SaProt	LLR -6.96	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 4	GERP 1.8, phastCons 1
Overall
CADD	19.68	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 0.00267% African / African-American · 2/74,926 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000186% 3/1,613,810 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,463
European (non-Finnish)	8.47e-05%	1,179,990

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.Val386Ile
Coding: c.1156G>A
MANE Select: NM_004656
dbSNP: rs372213315
Type: single nucleotide variant
Location: chr3:52404547 (GRCh38)
Gene constraint: LOEUF 0.324 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.87 · 4 PDB
Residue 386: the 'disordered' region; a UniProt-annotated variant site (in tpds1)

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.Val386= Likely benign ★★ same residue
BAP1 p.Val386Phe 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

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-val386ile (accessed [today's date]).

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