Is BRCA1 p.Ala280fs (c.824_833dup) pathogenic?

BRCA1 p.Ala280fs (c.824833dup) is classified Pathogenic in BRCA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-03-04). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA1 p.Ala280fs (c.824_833dup)?

BRCA1 p.Ala280fs (c.824_833dup) is associated with hereditary neoplastic syndrome (ClinVar).

How common is BRCA1 p.Ala280fs (c.824_833dup) in the general population?

BRCA1 p.Ala280fs (c.824_833dup) is absent from gnomAD (gnomAD).

BRCA1 p.Ala280fs

c.824_833dup · rs2552228760 · VCV1762594

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 neoplastic 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 10 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4	GERP 1.4, 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.Ala280fs
Coding: c.824_833dup
MANE Select: NM_007294
dbSNP: rs2552228760
Type: Duplication
Location: chr17:43094697 (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 neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BRCA1 p.Ala280Gly Benign ★★★ ⚠ same residue
BRCA1 p.Ala280= Likely benign ★★ same residue
BRCA1 p.Ala280Asp Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 c.5155dup Pathogenic ★★★ same condition
BRCA1 p.Arg163fs Pathogenic ★★★ same condition
BRCA1 p.Arg504_Lys505insTer Pathogenic ★★★ same condition
BRCA1 p.Arg613fs Pathogenic ★★★ same condition
BRCA1 p.Asn1016fs 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-ala280fs (accessed [today's date]).

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