Is BRCA2 p.Ser270= (c.810A>G) pathogenic?

BRCA2 p.Ser270= (c.810A>G) is classified Likely benign in BRCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-31). Very rare (popmax 0.00225%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA2 p.Ser270= (c.810A>G)?

BRCA2 p.Ser270= (c.810A>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is BRCA2 p.Ser270= (c.810A>G) in the general population?

BRCA2 p.Ser270= (c.810A>G) is very rare (popmax 0.00225%, sas) (gnomAD).

BRCA2 p.Ser270=

c.810A>G · VCV4215159

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00225%, sas)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.3	GERP -4.2, phastCons 0.77
Overall
CADD	3.246	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00225% South Asian · 2/88,944 alleles

Filtering AF 0.000373% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00014%

Overall 0.000125% 2/1,604,174 alleles · very rare exomes 1/1,451,966 · genomes 1/152,208 · 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.Ser270=
Coding: c.810A>G
MANE Select: NM_000059
Type: single nucleotide variant
Location: chr13:32332288 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)

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

Similar variants

BRCA2 p.Ser270Ter Pathogenic ★★ same residue
BRCA2 p.Ser270Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Ser270Leu Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Ser270Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 c.316+1G>T Pathogenic ★★★ same condition
BRCA2 c.316+2T>C Pathogenic ★★★ same condition
BRCA2 c.316+5G>A Pathogenic ★★★ same condition
BRCA2 c.316+5G>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-ser270 (accessed [today's date]).

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