Is BRCA2 p.Arg3385fs (c.10154_10155del) pathogenic?

BRCA2 p.Arg3385fs (c.1015410155del) is classified Likely benign in BRCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-22). Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with BRCA2 p.Arg3385fs (c.10154_10155del)?

BRCA2 p.Arg3385fs (c.10154_10155del) is associated with hereditary breast ovarian cancer syndrome (ClinVar).

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.Arg3385fs

c.10154_10155del · VCV3660048

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

hereditary breast ovarian cancer syndrome

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	escapes	premature termination codon in the last exon (27 of 27) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.15	GERP -2.2

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

Variant & gene context

Gene: BRCA2
Protein: p.Arg3385fs
Coding: c.10154_10155del
MANE Select: NM_000059
Type: Deletion
Location: chr13:32398667 (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

hereditary breast ovarian cancer syndrome — 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.Arg3385= Likely benign ★★ same residue
BRCA2 p.Arg3385Cys Benign/Likely benign ★★ same residue
BRCA2 p.Arg3385His Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 c.5217_5224del Pathogenic ★★★ same condition
BRCA2 c.68-?_316+?del Pathogenic ★★★ same condition
BRCA2 c.8312del Pathogenic ★★★ same condition
BRCA2 c.8633-24_8634del Pathogenic ★★★ same condition
BRCA2 c.8756del 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-arg3385fs (accessed [today's date]).

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