Is BRCA1 p.Pro1749fs (c.5244dup) pathogenic?

BRCA1 p.Pro1749fs (c.5244dup) is classified Pathogenic in BRCA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-03). Absent from gnomAD; Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with BRCA1 p.Pro1749fs (c.5244dup)?

BRCA1 p.Pro1749fs (c.5244dup) is associated with hereditary breast ovarian cancer syndrome (ClinVar).

How common is BRCA1 p.Pro1749fs (c.5244dup) in the general population?

BRCA1 p.Pro1749fs (c.5244dup) 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.Pro1749fs

c.5244dup · rs2548416943 · VCV2693875

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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	predicted	premature termination codon in exon 19 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.6	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.Pro1749fs
Coding: c.5244dup
MANE Select: NM_007294
dbSNP: rs2548416943
Type: Duplication
Location: chr17:43057084 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB
Residue 1749: a UniProt-annotated variant site (in fancs); a UniProt-annotated variant site (in ovarian cancer; uncertain significance; abolishes acaca binding and strongly reduces brip1 binding); an α-helix

Full BRCA1 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

BRCA1 p.Pro1749_Lys1750delinsGln Uncertain significance ★ same residue
BRCA1 p.Pro1749Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Pro1749Leu Uncertain significance ★ ⚠ same residue
BRCA1 c.5155dup Pathogenic ★★★ same condition
BRCA1 p.Ala1279fs Pathogenic ★★★ same condition
BRCA1 p.Ala794fs Pathogenic ★★★ same condition
BRCA1 p.Arg1347fs Pathogenic ★★★ same condition
BRCA1 p.Arg613fs 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-pro1749fs (accessed [today's date]).

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