Is BRCA2 p.Ser2807Pro (c.8419T>C) pathogenic?

BRCA2 p.Ser2807Pro (c.8419T>C) is classified Conflicting classifications of pathogenicity in BRCA2 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-09-04). AlphaMissense: likely pathogenic (0.8636); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA2 p.Ser2807Pro (c.8419T>C)?

BRCA2 p.Ser2807Pro (c.8419T>C) is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome, BRCA2-related cancer predisposition (ClinVar).

How common is BRCA2 p.Ser2807Pro (c.8419T>C) in the general population?

BRCA2 p.Ser2807Pro (c.8419T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRCA2 p.Ser2807Pro (c.8419T>C)?

AlphaMissense predicts likely pathogenic (score 0.8636) — an in-silico prediction, not a clinical call.

BRCA2 p.Ser2807Pro

c.8419T>C · rs1555287637 · VCV441481

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.8636 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.8636	likely pathogenic · top 2% in BRCA2
REVEL	0.493	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.1	GERP 2, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 35 kb · p 0.00024 · regional, not allelic
Overall
CADD	25.1	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

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.Ser2807Pro
Coding: c.8419T>C
MANE Select: NM_000059
dbSNP: rs1555287637
Type: single nucleotide variant
Location: chr13:32370489 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 2807: 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 BRCA2-related cancer predisposition

Similar variants

BRCA2 p.Ser2807Ter Pathogenic ★★★ same residue
BRCA2 p.Ser2807= Benign ★★★ same residue
BRCA2 p.Ser2807Leu Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Ser2807fs Pathogenic ★★★ same residue
BRCA2 p.Ser2807del Uncertain significance ★★ 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

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-ser2807pro (accessed [today's date]).

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