Is BRCA2 p.Arg1997fs (c.5987dup) pathogenic?

BRCA2 p.Arg1997fs (c.5987dup) is classified Pathogenic/Likely pathogenic in BRCA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-02). Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA2 p.Arg1997fs (c.5987dup)?

BRCA2 p.Arg1997fs (c.5987dup) is associated with hereditary neoplastic syndrome (ClinVar).

BRCA2 p.Arg1997fs

c.5987dup · VCV3992751

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

hereditary neoplastic 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	predicted	premature termination codon in exon 11 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.4	GERP 0.53, phastCons 1

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

Variant & gene context

Gene: BRCA2
Protein: p.Arg1997fs
Coding: c.5987dup
MANE Select: NM_000059
Type: Duplication
Location: chr13:32340341 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 1997: 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

Similar variants

BRCA2 p.Arg1997Gly Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Arg1997Lys Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Ala127fs Pathogenic ★★★ same condition
BRCA2 p.Ala2951fs Pathogenic ★★★ same condition
BRCA2 p.Ala483fs Pathogenic ★★★ same condition
BRCA2 p.Ala843fs Pathogenic ★★★ same condition
BRCA2 p.Arg2112fs Pathogenic ★★★ same condition
BRCA2 p.Arg2799delinsSerTer 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-arg1997fs (accessed [today's date]).

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