Is BRCA2 p.Arg329= (c.987G>A) pathogenic?

BRCA2 p.Arg329= (c.987G>A) is classified Benign in BRCA2 (ClinVar, Expert panel, 17 submitters; last evaluated 2017-06-29). Rare (popmax 0.195%, sas); Associated with breast-ovarian cancer, familial, susceptibility to, 2.

What condition is associated with BRCA2 p.Arg329= (c.987G>A)?

BRCA2 p.Arg329= (c.987G>A) is associated with breast-ovarian cancer, familial, susceptibility to, 2, hereditary breast ovarian cancer syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BRCA2 p.Arg329= (c.987G>A) in the general population?

BRCA2 p.Arg329= (c.987G>A) is rare (popmax 0.195%, sas) (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.Arg329=

c.987G>A · rs561002197 · VCV219579

Benign Expert panel

Classification

Benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 17 submitters

gnomAD v4.1

Rare

rare (popmax 0.195%, sas)

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 2.9	GERP 0.51, phastCons 1
Overall
CADD	5.912	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.195% South Asian · 168/86,068 alleles

Filtering AF 0.171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.162%

Overall 0.0117% 186/1,592,942 alleles · rare exomes 174/1,440,844 · genomes 12/152,098 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.195%	512
Middle Eastern	0.0337%	2,968
Remaining individualsnot grpmax-eligible	0.0114%	8,794
European (non-Finnish)	0.000767%	130,443

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.Arg329=
Coding: c.987G>A
MANE Select: NM_000059
dbSNP: rs561002197
Type: single nucleotide variant
Location: chr13:32332465 (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

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 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.Arg329Ser Uncertain significance ★★ same residue
BRCA2 p.Arg329Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Arg329fs 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-arg329 (accessed [today's date]).

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