Is BRCA2 p.Asn1288= (c.3864T>C) pathogenic?

BRCA2 p.Asn1288= (c.3864T>C) is classified Likely benign in BRCA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-25). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA2 p.Asn1288= (c.3864T>C)?

BRCA2 p.Asn1288= (c.3864T>C) is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome (ClinVar).

How common is BRCA2 p.Asn1288= (c.3864T>C) in the general population?

BRCA2 p.Asn1288= (c.3864T>C) is absent from gnomAD v4.1 (gnomAD).

BRCA2 p.Asn1288=

c.3864T>C · rs2548527092 · VCV2710538

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.91	GERP -0.75, phastCons 0.34
Overall
CADD	0.448	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BRCA2
Protein: p.Asn1288=
Coding: c.3864T>C
MANE Select: NM_000059
dbSNP: rs2548527092
Type: single nucleotide variant
Location: chr13:32338219 (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

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary breast ovarian cancer syndrome

Similar variants

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.Asn1288fs Pathogenic ★★★ same residue
BRCA2 p.Asn1288Ter Pathogenic ★ same residue
BRCA2 p.Asn1288del Conflicting classifications of pathogenicity ★ same residue
BRCA2 c.316+1G>T 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-asn1288 (accessed [today's date]).

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