Is BRCA2 p.Ser973= (c.2919G>A) pathogenic?

BRCA2 p.Ser973= (c.2919G>A) is classified Benign in BRCA2 (ClinVar, Expert panel, 25 submitters; last evaluated 2017-06-29). Rare (popmax 0.215%, mid); Associated with breast-ovarian cancer, familial, susceptibility to, 2.

What condition is associated with BRCA2 p.Ser973= (c.2919G>A)?

BRCA2 p.Ser973= (c.2919G>A) is associated with breast-ovarian cancer, familial, susceptibility to, 2, hereditary breast ovarian cancer syndrome, breast cancer (ClinVar).

How common is BRCA2 p.Ser973= (c.2919G>A) in the general population?

BRCA2 p.Ser973= (c.2919G>A) is rare (popmax 0.215%, mid) (gnomAD).

How is Hereditary breast and/or ovarian cancer syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

BRCA2 p.Ser973=

c.2919G>A · rs45525041 · VCV51370

Benign Expert panel

Classification

Benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 25 submitters

gnomAD v4.1

Rare

rare (popmax 0.215%, mid)

Conditions

breast-ovarian cancer, familial, susceptibility to, 2

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 -0.3	GERP -4.5
Overall
CADD	1.028	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.215% Middle Eastern · 13/6,042 alleles

Filtering AF 0.127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.115%

Overall 0.0308% 496/1,611,690 alleles · rare exomes 472/1,459,544 · genomes 24/152,146 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.215%	465
South Asian	0.143%	701
Remaining individualsnot grpmax-eligible	0.0289%	3,465
European (non-Finnish)	0.0272%	3,674
Admixed American	0.0202%	4,963
East Asian	0.00446%	22,400
African / African-American	0.00134%	74,806

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.Ser973=
Coding: c.2919G>A
MANE Select: NM_000059
dbSNP: rs45525041
Type: single nucleotide variant
Location: chr13:32337274 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 973: the 'interaction with npm1' region

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

Disease context

breast-ovarian cancer, familial, susceptibility to, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary breast ovarian cancer syndrome breast cancer Fanconi anemia complementation group D1 hereditary neoplastic syndrome hereditary breast carcinoma

For Hereditary breast and/or ovarian cancer syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

BRCA2 p.Ser973Ter Pathogenic ★★★ same residue
BRCA2 p.Ser973Leu Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Ser973Trp 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
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-ser973 (accessed [today's date]).

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