Is BRCA1 p.Ala1175del (c.3521CTG[1]) pathogenic?

BRCA1 p.Ala1175del (c.3521CTG[1]) is classified Uncertain significance in BRCA1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-11-12). Very rare (popmax 8.47e-05%, nfe); Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with BRCA1 p.Ala1175del (c.3521CTG[1])?

BRCA1 p.Ala1175del (c.3521CTG[1]) is associated with hereditary breast ovarian cancer syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BRCA1 p.Ala1175del (c.3521CTG[1]) in the general population?

BRCA1 p.Ala1175del (c.3521CTG[1]) is very rare (popmax 8.47e-05%, 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.

BRCA1 p.Ala1175del

c.3521CTG[1] · rs1555587557 · VCV441378

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

hereditary breast ovarian cancer syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.4	GERP 2.5, phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,022 alleles

Overall 6.84e-05% 1/1,461,804 alleles · very rare

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: BRCA1
Protein: p.Ala1175del
Coding: c.3521CTG[1]
MANE Select: NM_007294
dbSNP: rs1555587557
Type: Microsatellite
Location: chr17:43092005 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB
Residue 1175: a UniProt-annotated variant site (in fancs)

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

Also linked: hereditary neoplastic syndrome

For Hereditary breast and/or ovarian cancer syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

BRCA1 p.Ala1175= Conflicting classifications of pathogenicity ★ same residue
BRCA1 p.Ala1175Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Ala1175Val Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Ala1082_Met1083insTer Pathogenic ★★★ same condition
BRCA1 p.Ala92fs Pathogenic ★★★ same condition
BRCA1 p.Arg1583fs Pathogenic ★★★ same condition
BRCA1 p.Arg350fs Pathogenic ★★★ same condition
BRCA1 p.Asn363fs 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-ala1175del (accessed [today's date]).

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