Is BRCA1 p.Ala1293Phe (c.3877_3878delinsTT) pathogenic?

BRCA1 p.Ala1293Phe (c.38773878delinsTT) is classified Conflicting classifications of pathogenicity in BRCA1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2023-03-23). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA1 p.Ala1293Phe (c.3877_3878delinsTT)?

BRCA1 p.Ala1293Phe (c.3877_3878delinsTT) is associated with hereditary neoplastic syndrome (ClinVar).

How common is BRCA1 p.Ala1293Phe (c.3877_3878delinsTT) in the general population?

BRCA1 p.Ala1293Phe (c.3877_3878delinsTT) is absent from gnomAD (gnomAD).

BRCA1 p.Ala1293Phe

c.3877_3878delinsTT · rs2552130085 · VCV1735756

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary neoplastic 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 0.4	GERP -4.1, phastCons 0.001
Regional constraint	o/e 0.91	unconstrained · MANE · 78 kb · p 4.8e-05 · regional, not allelic

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.Ala1293Phe
Coding: c.3877_3878delinsTT
MANE Select: NM_007294
dbSNP: rs2552130085
Type: Indel
Location: chr17:43091653 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB
Residue 1293: a UniProt-annotated variant site (in fancs)

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.Ala1293Asp Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Ala1293Pro Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Ala1293Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Ala1293Val Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 c.4185+2_4185+22delinsA Pathogenic ★★★ same condition
BRCA1 p.Ala1293fs Pathogenic ★★★ same residue
BRCA1 p.Ala521_Asp522delinsTer Pathogenic ★★★ same condition
BRCA1 p.Asn1592fs 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-ala1293phe (accessed [today's date]).

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