Is BRCA2 p.Met2676Val (c.8026A>G) pathogenic?

BRCA2 p.Met2676Val (c.8026A>G) is classified Uncertain significance in BRCA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-23). AlphaMissense: likely benign (0.1029); Absent from gnomAD v4.1; Associated with BRCA2-related cancer predisposition.

What condition is associated with BRCA2 p.Met2676Val (c.8026A>G)?

BRCA2 p.Met2676Val (c.8026A>G) is associated with BRCA2-related cancer predisposition, hereditary breast ovarian cancer syndrome (ClinVar).

How common is BRCA2 p.Met2676Val (c.8026A>G) in the general population?

BRCA2 p.Met2676Val (c.8026A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRCA2 p.Met2676Val (c.8026A>G)?

AlphaMissense predicts likely benign (score 0.1029) — an in-silico prediction, not a clinical call.

BRCA2 p.Met2676Val

c.8026A>G · rs878853607 · VCV236912

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1029 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,614,018)

Conditions

BRCA2-related cancer predisposition

Computational evidence

Protein change
AlphaMissense	0.1029	likely benign
REVEL	0.476	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.97	GERP -1.5
Regional constraint	o/e 1.03	unconstrained · MANE · 47 kb · p 0.059 · regional, not allelic
Overall
CADD	10.55	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

No allele count reported in gnomAD v4.1 (AN 1,614,018). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BRCA2
Protein: p.Met2676Val
Coding: c.8026A>G
MANE Select: NM_000059
dbSNP: rs878853607
Type: single nucleotide variant
Location: chr13:32363228 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 2676: the 'interaction with sem1' region

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

Disease context

Also linked: hereditary breast ovarian cancer syndrome

Similar variants

BRCA2 p.Met2676Thr Benign/Likely benign ★★ same residue
BRCA2 p.Met2676Leu Uncertain significance ★ same residue
BRCA2 c.316+2T>C Pathogenic ★★★ same condition
BRCA2 c.316+5G>A Pathogenic ★★★ same condition
BRCA2 c.316+5G>C Pathogenic ★★★ same condition
BRCA2 c.475+1G>A Pathogenic ★★★ same condition
BRCA2 c.475+1G>T Pathogenic ★★★ same condition
BRCA2 c.476-2A>G 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/brca2-p-met2676val (accessed [today's date]).

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