Is BRCA1 p.Arg1751fs (c.5251del) pathogenic?

BRCA1 p.Arg1751fs (c.5251del) is classified Pathogenic in BRCA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-02). Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA1 p.Arg1751fs (c.5251del)?

BRCA1 p.Arg1751fs (c.5251del) is associated with hereditary neoplastic syndrome (ClinVar).

BRCA1 p.Arg1751fs

c.5251del · VCV3992584

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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 19 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.7	GERP 1.6, phastCons 1

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

Variant & gene context

Gene: BRCA1
Protein: p.Arg1751fs
Coding: c.5251del
MANE Select: NM_007294
Type: Deletion
Location: chr17:43057078 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB
Residue 1751: a UniProt-annotated variant site (in fancs); an α-helix

Full BRCA1 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

BRCA1 p.Arg1751Pro Likely pathogenic ★★★ same residue
BRCA1 p.Arg1751Ter Pathogenic ★★★ same residue
BRCA1 p.Arg1751Gln Benign ★★★ ⚠ same residue
BRCA1 p.Arg1751Leu Uncertain significance ★★ ⚠ same residue
BRCA1 p.Arg1751= Likely benign ★★ same residue
BRCA1 c.302-2del Pathogenic ★★★ same condition
BRCA1 c.442-22_442-13del Pathogenic ★★★ same condition
BRCA1 c.5277+1_5277+6del 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/brca1-p-arg1751fs (accessed [today's date]).

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