Is BRCA2 p.Arg3370Ter (c.10107dup) pathogenic?

BRCA2 p.Arg3370Ter (c.10107dup) is classified Likely benign in BRCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-20). Very rare (popmax 0.000254%, nfe); Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with BRCA2 p.Arg3370Ter (c.10107dup)?

BRCA2 p.Arg3370Ter (c.10107dup) is associated with hereditary breast ovarian cancer syndrome (ClinVar).

How common is BRCA2 p.Arg3370Ter (c.10107dup) in the general population?

BRCA2 p.Arg3370Ter (c.10107dup) is very rare (popmax 0.000254%, nfe) (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.Arg3370Ter

c.10107dup · rs2548565619 · VCV2110628

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

hereditary breast ovarian cancer syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	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 0.7	GERP -0.4

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,912 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,614,058 alleles · very rare exomes 3/1,461,744 · genomes 0/152,314 · joint denominator

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.Arg3370Ter
Coding: c.10107dup
MANE Select: NM_000059
dbSNP: rs2548565619
Type: Duplication
Location: chr13:32398619 (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.Arg3370= Benign ★★★ same residue
BRCA2 c.1448_1451dupCAGT Pathogenic ★★★ same condition
BRCA2 c.6081dupA Pathogenic ★★★ same condition
BRCA2 c.6396dupA Pathogenic ★★★ same condition
BRCA2 c.6528_6535dup Pathogenic ★★★ same condition
BRCA2 p.Ala2951fs Pathogenic ★★★ same condition
BRCA2 p.Ala483fs Pathogenic ★★★ same condition
BRCA2 p.Arg2112fs 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-arg3370ter (accessed [today's date]).

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