Is BRCA1 p.Arg1753fs (c.5257dup) pathogenic?

BRCA1 p.Arg1753fs (c.5257dup) is classified Pathogenic in BRCA1 (ClinVar, Expert panel, 2 submitters; last evaluated 2016-10-18). Absent from gnomAD; Associated with breast-ovarian cancer, familial, susceptibility to, 1.

What condition is associated with BRCA1 p.Arg1753fs (c.5257dup)?

BRCA1 p.Arg1753fs (c.5257dup) is associated with breast-ovarian cancer, familial, susceptibility to, 1 (ClinVar).

How common is BRCA1 p.Arg1753fs (c.5257dup) in the general population?

BRCA1 p.Arg1753fs (c.5257dup) 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.

BRCA1 p.Arg1753fs

c.5257dup · rs397509245 · VCV55486

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, 1

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 7.4	GERP 1.6, phastCons 1

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: BRCA1
Protein: p.Arg1753fs
Coding: c.5257dup
MANE Select: NM_007294
dbSNP: rs397509245
Type: Duplication
Location: chr17:43057071 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB
Residue 1753: a UniProt-annotated variant site (in fancs); a UniProt-annotated variant site (in bc; uncertain significance); an α-helix

Full BRCA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

breast-ovarian cancer, familial, susceptibility to, 1 — 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

BRCA1 p.Arg1753= Likely benign ★★★ same residue
BRCA1 c.4186-1787_4358-1668dup Pathogenic ★★★ same condition
BRCA1 c.5155dup Pathogenic ★★★ same condition
BRCA1 p.Ala1070delinsValLeuMetLysTrpAlaProValLeuMetLysTer Pathogenic ★★★ same condition
BRCA1 p.Ala1279fs Pathogenic ★★★ same condition
BRCA1 p.Ala1615fs Pathogenic ★★★ same condition
BRCA1 p.Ala1627fs Pathogenic ★★★ same condition
BRCA1 p.Ala1823fs 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-arg1753fs (accessed [today's date]).

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