Is BRCA2 p.Ile383= (c.1149C>A) pathogenic?

BRCA2 p.Ile383= (c.1149C>A) is classified Likely benign in BRCA2 (ClinVar, Expert panel, 3 submitters; last evaluated 2017-06-29). Absent from gnomAD v4.1; Associated with breast-ovarian cancer, familial, susceptibility to, 2.

What condition is associated with BRCA2 p.Ile383= (c.1149C>A)?

BRCA2 p.Ile383= (c.1149C>A) is associated with breast-ovarian cancer, familial, susceptibility to, 2, hereditary breast ovarian cancer syndrome (ClinVar).

How common is BRCA2 p.Ile383= (c.1149C>A) in the general population?

BRCA2 p.Ile383= (c.1149C>A) is absent from gnomAD v4.1 (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.Ile383=

c.1149C>A · rs80359780 · VCV51072

Likely benign Expert panel

Classification

Likely benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 3 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.21	GERP -2.4
Overall
CADD	5.467	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.Ile383=
Coding: c.1149C>A
MANE Select: NM_000059
dbSNP: rs80359780
Type: single nucleotide variant
Location: chr13:32332627 (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

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

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

BRCA2 p.Ile383Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Ile383fs Pathogenic ★★★ same residue
BRCA2 p.Ile383Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Ile383Val Likely benign ★ 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-ile383 (accessed [today's date]).

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