Is BAP1 p.Glu315Ala (c.944A>C) pathogenic?

BAP1 p.Glu315Ala (c.944A>C) is classified Conflicting classifications of pathogenicity in BAP1 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-24). AlphaMissense: likely benign (0.0797); Ultra-rare (popmax 0.0166%, mid); Associated with BAP1-related tumor predisposition syndrome.

What condition is associated with BAP1 p.Glu315Ala (c.944A>C)?

BAP1 p.Glu315Ala (c.944A>C) is associated with BAP1-related tumor predisposition syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BAP1 p.Glu315Ala (c.944A>C) in the general population?

BAP1 p.Glu315Ala (c.944A>C) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

How is BAP1-related tumor predisposition syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about BAP1 p.Glu315Ala (c.944A>C)?

AlphaMissense predicts likely benign (score 0.0797) — an in-silico prediction, not a clinical call.

BAP1 p.Glu315Ala

c.944A>C · rs149974450 · VCV412406

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0797 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

BAP1-related tumor predisposition syndrome

Computational evidence

Protein change
AlphaMissense	0.0797	likely benign
REVEL	0.08	moderately benign-leaning
SaProt	LLR -5.63	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.28 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.1	GERP 1.9, phastCons 1
Overall
CADD	19.88	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 0.0166% Middle Eastern · 1/6,012 alleles

Filtering AF 0.00511% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.00552% 89/1,613,644 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,012
Admixed American	0.00833%	12,002
European (non-Finnish)	0.00627%	15,946
East Asian	0.00446%	22,438
South Asian	0.00329%	30,357
Finnishnot grpmax-eligible	0.00314%	31,853
Remaining individualsnot grpmax-eligible	0.0016%	62,494
African / African-American	0.00133%	74,964

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.Glu315Ala
Coding: c.944A>C
MANE Select: NM_007212 · reported on NM_004656
dbSNP: rs149974450
Type: single nucleotide variant
Location: chr3:52405282 (GRCh38)
Structure: AlphaFold pLDDT 78.27 · 28 PDB
Residue 315: an α-helix

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

Disease context

Also linked: hereditary neoplastic syndrome

For BAP1-related tumor predisposition syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

BAP1 p.Glu315= Likely benign ★★ same residue
BAP1 p.Glu315Lys 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-glu315ala (accessed [today's date]).

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