Is BRCA1 p.Asn354fs (c.1061del) pathogenic?

BRCA1 p.Asn354fs (c.1061del) is classified Likely pathogenic in BRCA1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-09-12). Absent from gnomAD; Associated with breast carcinoma.

What condition is associated with BRCA1 p.Asn354fs (c.1061del)?

BRCA1 p.Asn354fs (c.1061del) is associated with breast carcinoma (ClinVar).

How common is BRCA1 p.Asn354fs (c.1061del) in the general population?

BRCA1 p.Asn354fs (c.1061del) is absent from gnomAD (gnomAD).

BRCA1 p.Asn354fs

c.1061del · rs2154478354 · VCV1244222

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

breast carcinoma

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 0.63	GERP -5

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.Asn354fs
Coding: c.1061del
MANE Select: NM_007294
dbSNP: rs2154478354
Type: Deletion
Location: chr17:43094470 (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

breast carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BRCA1 p.Asn1265fs Pathogenic ★★★ same condition
BRCA1 p.Asn1354fs Pathogenic ★★★ same condition
BRCA1 p.Gly1748fs Pathogenic ★★★ same condition
BRCA1 p.Val1607fs Pathogenic ★ same condition
BRCA1 p.Asn354Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Asn354Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 c.473_547+288del Likely pathogenic same condition
BRCA1 p.Pro919fs Likely 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-asn354fs (accessed [today's date]).

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