Is BRCA2 p.Asn1288del (c.3861TAA[1]) pathogenic?

BRCA2 p.Asn1288del (c.3861TAA[1]) is classified Conflicting classifications of pathogenicity in BRCA2 (ClinVar, Conflicting submitters, 17 submitters; last evaluated 2026-07-29). Very rare (popmax 0.00139%, afr); Associated with BRCA2-related cancer predisposition.

What condition is associated with BRCA2 p.Asn1288del (c.3861TAA[1])?

BRCA2 p.Asn1288del (c.3861TAA[1]) is associated with BRCA2-related cancer predisposition, hereditary breast ovarian cancer syndrome, breast-ovarian cancer, familial, susceptibility to, 2 (ClinVar).

How common is BRCA2 p.Asn1288del (c.3861TAA[1]) in the general population?

BRCA2 p.Asn1288del (c.3861TAA[1]) is very rare (popmax 0.00139%, afr) (gnomAD).

BRCA2 p.Asn1288del

c.3861TAA[1] · rs276174837 · VCV126027

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 17 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00139%, afr)

Conditions

BRCA2-related cancer predisposition

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 3.1	GERP -0.55, phastCons 0.97
Overall
CADD	0.356	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00139% African / African-American · 1/71,832 alleles

Filtering AF 0.000189% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000124%

Overall 0.000453% 7/1,544,010 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00139%	71,832
European (non-Finnish)	0.000525%	190,639

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.Asn1288del
Coding: c.3861TAA[1]
MANE Select: NM_000059
dbSNP: rs276174837
Type: Microsatellite
Location: chr13:32338214 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 1288: the 'interaction with rad51' region

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

Disease context

Also linked: hereditary breast ovarian cancer syndrome breast-ovarian cancer, familial, susceptibility to, 2 hereditary neoplastic syndrome

Similar variants

BRCA2 p.Asn1288fs Pathogenic ★★★ same residue
BRCA2 p.Asn1288= Likely benign ★★ same residue
BRCA2 p.Asn1288Ter Pathogenic ★ same residue
BRCA2 p.Asn1288Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Asn1288Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Asn1288Asp Likely benign ★ same residue
BRCA2 p.Asn1288His Likely benign ★ same residue
BRCA2 p.Ala1439fs 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-asn1288del (accessed [today's date]).

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