Is BRCA1 p.Ala134Phe (c.400_401delinsTT) pathogenic?

BRCA1 p.Ala134Phe (c.400401delinsTT) is classified Uncertain significance in BRCA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-01). Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with BRCA1 p.Ala134Phe (c.400_401delinsTT)?

BRCA1 p.Ala134Phe (c.400_401delinsTT) is associated with hereditary breast ovarian cancer syndrome (ClinVar).

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.Ala134Phe

c.400_401delinsTT · VCV4732287

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

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 1.6	GERP 0.018, phastCons 0.91
Regional constraint	o/e 0.91	unconstrained · MANE · 78 kb · p 4.8e-05 · regional, not allelic

Variant & gene context

Gene: BRCA1
Protein: p.Ala134Phe
Coding: c.400_401delinsTT
MANE Select: NM_007294
Type: Indel
Location: chr17:43104162 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB

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.Ala134_Lys135insThr Uncertain significance ★★ same residue
BRCA1 p.Ala134Asp Uncertain significance ★★ ⚠ same residue
BRCA1 p.Ala134Thr Uncertain significance ★★ ⚠ same residue
BRCA1 c.4185+2_4185+22delinsA Pathogenic ★★★ same condition
BRCA1 p.Ala134fs Pathogenic ★★★ same residue
BRCA1 p.Ala521_Asp522delinsTer Pathogenic ★★★ same condition
BRCA1 p.Ala521Ter Pathogenic ★★★ same condition
BRCA1 p.Asn417fs 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-ala134phe (accessed [today's date]).

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