Is BRCA1 p.Ala1039fs (c.3114_3117delinsGA) pathogenic?

BRCA1 p.Ala1039fs (c.31143117delinsGA) is classified Pathogenic in BRCA1 (ClinVar, Expert panel, 3 submitters; last evaluated 2016-09-08). Absent from gnomAD; Associated with breast-ovarian cancer, familial, susceptibility to, 1.

What condition is associated with BRCA1 p.Ala1039fs (c.3114_3117delinsGA)?

BRCA1 p.Ala1039fs (c.3114_3117delinsGA) is associated with breast-ovarian cancer, familial, susceptibility to, 1 (ClinVar).

How common is BRCA1 p.Ala1039fs (c.3114_3117delinsGA) in the general population?

BRCA1 p.Ala1039fs (c.3114_3117delinsGA) 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.Ala1039fs

c.3114_3117delinsGA · rs273899700 · VCV125607

Pathogenic Expert panel

Classification

Pathogenic

ClinVar

Review

Expert panel ★★★☆

ClinVar · 3 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 10 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.77	GERP -1.5, phastCons 0.001

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.Ala1039fs
Coding: c.3114_3117delinsGA
MANE Select: NM_007294
dbSNP: rs273899700
Type: Indel
Location: chr17:43092414 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB
Residue 1039: a UniProt-annotated variant site (in fancs)

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.Ala1039Gly Likely benign ★ same residue
BRCA1 c.4185+2_4185+22delinsA Pathogenic ★★★ same condition
BRCA1 c.5331_5332+1delinsCAACAT Pathogenic ★★★ same condition
BRCA1 p.Ala521_Asp522delinsTer Pathogenic ★★★ same condition
BRCA1 p.Ala521Ter Pathogenic ★★★ same condition
BRCA1 p.Arg1737fs Pathogenic ★★★ same condition
BRCA1 p.Asn1592fs 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-ala1039fs (accessed [today's date]).

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