Is BAP1 p.Arg264Thr (c.791G>C) pathogenic?

BAP1 p.Arg264Thr (c.791G>C) is classified Conflicting classifications of pathogenicity in BAP1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-12-29). AlphaMissense: likely pathogenic (0.6987); Very rare (popmax 0.00415%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with BAP1 p.Arg264Thr (c.791G>C)?

BAP1 p.Arg264Thr (c.791G>C) is associated with hereditary neoplastic syndrome, BAP1-related tumor predisposition syndrome (ClinVar).

How common is BAP1 p.Arg264Thr (c.791G>C) in the general population?

BAP1 p.Arg264Thr (c.791G>C) is very rare (popmax 0.00415%, nfe) (gnomAD).

What do computational predictors say about BAP1 p.Arg264Thr (c.791G>C)?

AlphaMissense predicts likely pathogenic (score 0.6987) — an in-silico prediction, not a clinical call.

BAP1 p.Arg264Thr

c.791G>C · rs978943999 · VCV846072

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.6987 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00415%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.6987	likely pathogenic
REVEL	0.164	moderately benign-leaning
SaProt	LLR -5.61	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	Δ0.27	acceptor gain · deltas
Pangolin	Δ0.21	gain · loss 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Overall
CADD	32.0	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 0.00415% European (non-Finnish) · 49/1,180,060 alleles

Filtering AF 0.00318% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00286%

Overall 0.00316% 51/1,613,982 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00415%	24,083
Remaining individualsnot grpmax-eligible	0.0016%	62,480
African / African-American	0.00133%	74,934

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.Arg264Thr
Coding: c.791G>C
MANE Select: NM_007212 · reported on NM_004656
dbSNP: rs978943999
Type: single nucleotide variant
Location: chr3:52405905 (GRCh38)
Structure: AlphaFold pLDDT 78.27 · 28 PDB
Residue 264: 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.Arg264= Benign/Likely benign ★★ same residue
BAP1 p.Arg264fs Pathogenic ★ same residue
RNF2 p.Ala264Thr 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

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-arg264thr (accessed [today's date]).

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