Is BRCA2 p.Asp244fs (c.729_730insC) pathogenic?

BRCA2 p.Asp244fs (c.729730insC) is classified Pathogenic in BRCA2 (ClinVar, Expert panel, 2 submitters; last evaluated 2016-10-18). Absent from gnomAD; Associated with breast-ovarian cancer, familial, susceptibility to, 2.

What condition is associated with BRCA2 p.Asp244fs (c.729_730insC)?

BRCA2 p.Asp244fs (c.729_730insC) is associated with breast-ovarian cancer, familial, susceptibility to, 2 (ClinVar).

How common is BRCA2 p.Asp244fs (c.729_730insC) in the general population?

BRCA2 p.Asp244fs (c.729_730insC) is absent from gnomAD (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.Asp244fs

c.729_730insC · rs1555281463 · VCV266999

Pathogenic Expert panel

Classification

Pathogenic

ClinVar

Review

Expert panel ★★★☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 9 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.3	GERP -1.6, phastCons 0.85

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BRCA2
Protein: p.Asp244fs
Coding: c.729_730insC
MANE Select: NM_000059
dbSNP: rs1555281463
Type: Insertion
Location: chr13:32330966 (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

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

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

BRCA2 p.Asp244Ter Pathogenic ★★★ same residue
BRCA2 p.Asp244Asn Uncertain significance ★★ ⚠ same residue
BRCA2 c.156_157insAlu Pathogenic ★★★ same condition
BRCA2 p.Ala1327fs Pathogenic ★★★ same condition
BRCA2 p.Ala1411fs Pathogenic ★★★ same condition
BRCA2 p.Ala1825fs Pathogenic ★★★ same condition
BRCA2 p.Ala1996fs Pathogenic ★★★ same condition
BRCA2 p.Ala2534fs 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-asp244fs (accessed [today's date]).

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