Is BRCA1 p.Gln1424fs (c.4271_4295del) pathogenic?

BRCA1 p.Gln1424fs (c.42714295del) is classified Pathogenic/Likely pathogenic in BRCA1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-13). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA1 p.Gln1424fs (c.4271_4295del)?

BRCA1 p.Gln1424fs (c.4271_4295del) is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome (ClinVar).

How common is BRCA1 p.Gln1424fs (c.4271_4295del) in the general population?

BRCA1 p.Gln1424fs (c.4271_4295del) is absent from gnomAD (gnomAD).

BRCA1 p.Gln1424fs

c.4271_4295del · rs2053050323 · VCV993204

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

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 12 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.6	GERP -5.2

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.Gln1424fs
Coding: c.4271_4295del
MANE Select: NM_007294
dbSNP: rs2053050323
Type: Deletion
Location: chr17:43082466 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB
Residue 1424: the 'interaction with palb2' region; 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

Also linked: hereditary breast ovarian cancer syndrome

Similar variants

BRCA1 p.Gln1424Ter Pathogenic ★★★ same residue
BRCA1 p.Gln1424His Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 c.302-2del Pathogenic ★★★ same condition
BRCA1 c.442-22_442-13del Pathogenic ★★★ same condition
BRCA1 c.4484+1del Pathogenic ★★★ same condition
BRCA1 c.5277+1_5277+6del Pathogenic ★★★ same condition
BRCA1 c.5278-2del Pathogenic ★★★ same condition
BRCA1 c.5333-36_5406+400del 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-gln1424fs (accessed [today's date]).

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