CHEK2 p.Arg145Pro
c.434G>C · rs587781667 · VCV584522
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9996 | likely pathogenic · top 1% in CHEK2 |
|---|---|---|
| REVEL | 0.844 | moderately pathogenic-leaning |
| SaProt | LLR -17.31 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.6 | GERP 1.7, phastCons 1 |
| Regional constraint | o/e 1.02 | unconstrained · MANE · 47 kb · p 0.57 · regional, not allelic |
| Overall | ||
| CADD | 32.0 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0022% | 45,542 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,504 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- CHEK2
- Protein
- p.Arg145Pro
- Coding
- c.434G>C
- MANE Select
- NM_007194
- dbSNP
- rs587781667
- Type
- single nucleotide variant
- Location
- chr22:28725253 (GRCh38)
- Gene constraint
- LOEUF 1.399 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 77.64 · 38 PDB
- Residue 145
- the fha domain; a UniProt-annotated variant site (in prostate cancer; somatic mutation); a UniProt-annotated variant site (in tpds4; loss of the ability to interact with and phosphorylate cdc25a and to promote cdc25a degradation in response to ionizing radiation); a β-strand
Similar variants
- CHEK2 p.Arg145Trp Likely pathogenic ★★ same residue
- CHEK2 p.Arg145Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
- CHEK2 p.Arg145Gly Uncertain significance ★ ⚠ same residue
- CHEK2 p.Arg145= Likely benign ★ same residue
- CHEK2 p.Arg145fs Pathogenic ★★ same residue
- CHEK2 c.1008+1G>A Likely pathogenic ★★ same condition
- CHEK2 c.1008+1G>T Likely pathogenic ★★ same condition
- CHEK2 c.1008+2T>A 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-arg145pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown