Is BRCA2 p.Asp1923Ala (c.5768A>C) pathogenic?

BRCA2 p.Asp1923Ala (c.5768A>C) is classified Benign in BRCA2 (ClinVar, Expert panel, 26 submitters; last evaluated 2019-06-18). AlphaMissense: likely benign (0.1366); Rare (popmax 0.331%, afr); Associated with breast-ovarian cancer, familial, susceptibility to, 2.

What condition is associated with BRCA2 p.Asp1923Ala (c.5768A>C)?

BRCA2 p.Asp1923Ala (c.5768A>C) is associated with breast-ovarian cancer, familial, susceptibility to, 2, hereditary breast ovarian cancer syndrome, breast cancer (ClinVar).

How common is BRCA2 p.Asp1923Ala (c.5768A>C) in the general population?

BRCA2 p.Asp1923Ala (c.5768A>C) is rare (popmax 0.331%, afr) (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.

What do computational predictors say about BRCA2 p.Asp1923Ala (c.5768A>C)?

AlphaMissense predicts likely benign (score 0.1366) — an in-silico prediction, not a clinical call.

BRCA2 p.Asp1923Ala

c.5768A>C · rs45491005 · VCV37995

Benign Expert panel

Classification

Benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 26 submitters

AlphaMissense

likely benign

0.1366 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.331%, afr)

Conditions

breast-ovarian cancer, familial, susceptibility to, 2

Computational evidence

Protein change
AlphaMissense	0.1366	likely benign
REVEL	0.458	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.55	GERP -4.6
Regional constraint	o/e 1.03	unconstrained · MANE · 47 kb · p 0.059 · regional, not allelic
Overall
CADD	7.777	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 0.331% African / African-American · 248/74,992 alleles

Filtering AF 0.297% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.284%

Overall 0.0159% 257/1,613,272 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.331%	302
Remaining individualsnot grpmax-eligible	0.00801%	12,491
Admixed American	0.00668%	14,973

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.Asp1923Ala
Coding: c.5768A>C
MANE Select: NM_000059
dbSNP: rs45491005
Type: single nucleotide variant
Location: chr13:32340123 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 1923: the 'interaction with rad51' 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 hereditary neoplastic syndrome BRCA2-related cancer predisposition

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

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

BRCA2 p.Asp1923= Likely benign ★★★ same residue
BRCA2 p.Asp1923Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Asp1923Glu Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Asp1923Val 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-asp1923ala (accessed [today's date]).

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