CHEK2 p.Pro393fs
c.1178_1187del · VCV4725103
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
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 11 of 15 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 0.75 | GERP -2.6, phastCons 0.006 |
| Region caveats | ||
| Repeat context | seg dup | · reads may not map uniquely · confidence, not pathogenicity |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- CHEK2
- Protein
- p.Pro393fs
- Coding
- c.1178_1187del
- MANE Select
- NM_007194
- Type
- Deletion
- Location
- chr22:28695782 (GRCh38)
- Gene constraint
- LOEUF 1.399 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 77.64 · 38 PDB
- Residue 393
- an α-helix; the protein kinase domain; the 't-loop/activation segment' region
Disease context
hereditary breast carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Hereditary breast cancer (Orphanet):
- Inheritance
- Autosomal dominant, Multigenic/multifactorial
- Onset
- Adult, Elderly
Similar variants
- CHEK2 p.Pro393Arg Uncertain significance ★★ ⚠ same residue
- CHEK2 p.Pro393Leu Uncertain significance ★★ ⚠ same residue
- CHEK2 p.Pro393Ser Uncertain significance ★★ ⚠ same residue
- CHEK2 p.Pro393= Likely benign ★★ same residue
- CHEK2 p.Pro393_Val395del Uncertain significance ★ same residue
- CHEK2 c.1096-3_1098del Likely pathogenic ★★ same condition
- CHEK2 c.1375+1_1375+2del Likely pathogenic ★★ same condition
- CHEK2 c.1375+1del 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/chek2-p-pro393fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown