BRCA1 p.Pro981fs
c.2940_2941insNNNNNNNNNNNNNNNN · VCV3893006
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
3
hereditary 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 3.8 | GERP 0.39, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- BRCA1
- Protein
- p.Pro981fs
- Coding
- c.2940_2941insNNNNNNNNNNNNNNNN
- MANE Select
- NM_007294
- Type
- Insertion
- Location
- chr17:43092590 (GRCh38)
- Gene constraint
- LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 41.99 · 33 PDB
- Residue 981
- a UniProt-annotated variant site (in fancs)
Disease context
hereditary breast carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: breast-ovarian cancer, familial, susceptibility to, 1Fanconi anemia, complementation group S
For Hereditary breast cancer (Orphanet):
- Inheritance
- Autosomal dominant, Multigenic/multifactorial
- Onset
- Adult, Elderly
Similar variants
- BRCA1 p.Pro981= Likely benign ★★★ same residue
- BRCA1 p.Pro981Ala Likely benign same residue
- BRCA1 p.Ala302fs Pathogenic ★★★ same condition
- BRCA1 p.Ala407fs Pathogenic ★★★ same condition
- BRCA1 p.Ala883fs Pathogenic ★★★ same condition
- BRCA1 p.Ala887fs Pathogenic ★★★ same condition
- BRCA1 p.Arg951fs Pathogenic ★★★ same condition
- BRCA1 p.Asn244delinsSerAsnLysTyrTer 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-pro981fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown