CHEK2 p.Ser73fs
c.217del · VCV4071204
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 2 of 15 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 9.6 | GERP 0.51, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- CHEK2
- Protein
- p.Ser73fs
- Coding
- c.217del
- MANE Select
- NM_007194
- Type
- Deletion
- Location
- chr22:28734505 (GRCh38)
- Gene constraint
- LOEUF 1.399 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 77.64 · 38 PDB
- Residue 73
- a modified residue (phosphoserine; by plk3)
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.Ser73_Ile74insTer Pathogenic/Likely pathogenic ★★ same residue
- CHEK2 p.Ser73Cys Uncertain significance ★★ ⚠ same residue
- CHEK2 p.Ser73Ala Uncertain significance ★ ⚠ same residue
- CHEK2 p.Ser73Pro 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
- CHEK2 c.1461+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-ser73fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown