Is BRCA2 p.Asp2811Glu (c.8433T>G) pathogenic?

BRCA2 p.Asp2811Glu (c.8433T>G) is classified Uncertain significance in BRCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-04). AlphaMissense: likely benign (0.1376); Absent from gnomAD v4.1.

How common is BRCA2 p.Asp2811Glu (c.8433T>G) in the general population?

BRCA2 p.Asp2811Glu (c.8433T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRCA2 p.Asp2811Glu (c.8433T>G)?

AlphaMissense predicts likely benign (score 0.1376) — an in-silico prediction, not a clinical call.

BRCA2 p.Asp2811Glu

c.8433T>G · VCV3256258

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1376 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.1376	likely benign
REVEL	0.358	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2.1	GERP -3.9
Regional constraint	o/e 0.87	unconstrained · MANE · 35 kb · p 0.00024 · regional, not allelic
Overall
CADD	3.638	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BRCA2
Protein: p.Asp2811Glu
Coding: c.8433T>G
MANE Select: NM_000059
Type: single nucleotide variant
Location: chr13:32370503 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 2811: the 'interaction with sem1' region

Full BRCA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BRCA2 p.Asp2811Gly Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Asp2811His Uncertain significance ★ same residue
BRCA2 p.Asp2811Val Uncertain significance ★ same residue
BRCA2 p.Asp2811= Likely benign ★ same residue
BRCA2 p.Asp2811Asn Likely benign ★ same residue
BRCA2 p.Asp2811fs Pathogenic ★ same residue
BRCA2 c.316+1G>T Pathogenic ★★★ same type
BRCA2 c.316+2T>C Pathogenic ★★★ same type

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/brca2-p-asp2811glu (accessed [today's date]).

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