Is BRCA2 p.Asn1279del (c.3835_3837del) pathogenic?

BRCA2 p.Asn1279del (c.38353837del) is classified Uncertain significance in BRCA2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-09-01). Very rare (popmax 0.0012%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA2 p.Asn1279del (c.3835_3837del)?

BRCA2 p.Asn1279del (c.3835_3837del) is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome, breast-ovarian cancer, familial, susceptibility to, 2 (ClinVar).

How common is BRCA2 p.Asn1279del (c.3835_3837del) in the general population?

BRCA2 p.Asn1279del (c.3835_3837del) is very rare (popmax 0.0012%, sas) (gnomAD).

BRCA2 p.Asn1279del

c.3835_3837del · rs864622459 · VCV220287

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0012%, sas)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.085	GERP -0.31

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0012% South Asian · 1/83,558 alleles

Overall 7.08e-05% 1/1,411,578 alleles · very rare

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.Asn1279del
Coding: c.3835_3837del
MANE Select: NM_000059
dbSNP: rs864622459
Type: Deletion
Location: chr13:32338188 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 1279: the 'interaction with rad51' region; a UniProt-annotated variant site (in)

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 breast-ovarian cancer, familial, susceptibility to, 2

Similar variants

BRCA2 p.Asn1279_Asp1280del Uncertain significance ★ same residue
BRCA2 p.Asn1279= Likely benign ★★ same residue
BRCA2 p.Asn1279fs Pathogenic ★ same residue
BRCA2 p.Asn1279Asp Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Asn1279Lys Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Asn1279Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 c.316+4del Pathogenic ★★★ same condition
BRCA2 c.5217_5224del 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-asn1279del (accessed [today's date]).

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