Is BRCA2 p.Ser2810Arg (c.8430T>G) pathogenic?

BRCA2 p.Ser2810Arg (c.8430T>G) is classified Conflicting classifications of pathogenicity in BRCA2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-08-13). AlphaMissense: ambiguous (0.3839); Very rare (popmax 8.48e-05%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA2 p.Ser2810Arg (c.8430T>G)?

BRCA2 p.Ser2810Arg (c.8430T>G) is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome (ClinVar).

How common is BRCA2 p.Ser2810Arg (c.8430T>G) in the general population?

BRCA2 p.Ser2810Arg (c.8430T>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about BRCA2 p.Ser2810Arg (c.8430T>G)?

AlphaMissense predicts ambiguous (score 0.3839) — an in-silico prediction, not a clinical call.

BRCA2 p.Ser2810Arg

c.8430T>G · rs876658487 · VCV230292

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.3839 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.3839	ambiguous
REVEL	0.492	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 -0.3	GERP -3.2, phastCons 0.38
Regional constraint	o/e 0.87	unconstrained · MANE · 35 kb · p 0.00024 · regional, not allelic
Overall
CADD	22.1	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

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,584 alleles

Overall 6.2e-05% 1/1,613,588 alleles · very rare exomes 0/1,461,394 · genomes 1/152,194 · joint denominator

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: BRCA2
Protein: p.Ser2810Arg
Coding: c.8430T>G
MANE Select: NM_000059
dbSNP: rs876658487
Type: single nucleotide variant
Location: chr13:32370500 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 2810: the 'interaction with sem1' region

Full BRCA2 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: hereditary breast ovarian cancer syndrome

Similar variants

BRCA2 p.Ser2810Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Ser2810Gly Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Ser2810Thr Uncertain significance ★ same residue
BRCA2 p.Ser2810= Likely benign ★ same residue
BRCA2 p.Ser2810Cys Likely benign ★ same residue
BRCA2 p.Ser2810fs Pathogenic ★★★ same residue
BRCA2 c.316+1G>T Pathogenic ★★★ same condition
BRCA2 c.316+2T>C 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-ser2810arg (accessed [today's date]).

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