Is BRCA2 p.Ser1882Pro (c.5644T>C) pathogenic?

BRCA2 p.Ser1882Pro (c.5644T>C) is classified Conflicting classifications of pathogenicity in BRCA2 (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2025-04-17). AlphaMissense: likely benign (0.0973); Very rare (popmax 0.00246%, nfe); Associated with Breast and/or ovarian cancer.

What condition is associated with BRCA2 p.Ser1882Pro (c.5644T>C)?

BRCA2 p.Ser1882Pro (c.5644T>C) is associated with Breast and/or ovarian cancer, hereditary breast ovarian cancer syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BRCA2 p.Ser1882Pro (c.5644T>C) in the general population?

BRCA2 p.Ser1882Pro (c.5644T>C) is very rare (popmax 0.00246%, nfe) (gnomAD).

What do computational predictors say about BRCA2 p.Ser1882Pro (c.5644T>C)?

AlphaMissense predicts likely benign (score 0.0973) — an in-silico prediction, not a clinical call.

BRCA2 p.Ser1882Pro

c.5644T>C · rs730881538 · VCV182219

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.0973 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00246%, nfe)

Conditions

Breast and/or ovarian cancer

Computational evidence

Protein change
AlphaMissense	0.0973	likely benign
REVEL	0.389	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.86	GERP -4.1, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 47 kb · p 0.059 · regional, not allelic
Overall
CADD	4.757	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00246% European (non-Finnish) · 29/1,179,526 alleles

Filtering AF 0.00172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.00205% 30/1,460,368 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00246%	40,673
Remaining individualsnot grpmax-eligible	0.0016%	62,456

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.Ser1882Pro
Coding: c.5644T>C
MANE Select: NM_000059
dbSNP: rs730881538
Type: single nucleotide variant
Location: chr13:32339999 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 1882: the 'interaction with rad51' region

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

Disease context

Breast and/or ovarian cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary breast ovarian cancer syndrome hereditary neoplastic syndrome

Similar variants

BRCA2 p.Ser1882Ter Pathogenic ★★★ same residue
BRCA2 p.Ser1882= Likely benign ★★★ same residue
BRCA2 p.Ser1882fs Pathogenic ★★★ 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
BRCA2 c.475+1G>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-ser1882pro (accessed [today's date]).

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