CHEK2 p.Arg148=
c.444G>A · rs1298109942 · VCV1005119
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
2
hereditary neoplastic syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.85 | donor gain · deltas |
|---|---|---|
| Pangolin | Δ0.73 | gain · loss 0.17 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 2.1 | GERP -1.8, phastCons 1 |
| Overall | ||
| CADD | 23.4 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- CHEK2
- Protein
- p.Arg148=
- Coding
- c.444G>A
- MANE Select
- NM_007194
- dbSNP
- rs1298109942
- Type
- single nucleotide variant
- Location
- chr22:28725243 (GRCh38)
- Gene constraint
- LOEUF 1.399 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 77.64 · 38 PDB
- Residue 148
- the fha domain; a β-strand
Similar variants
- CHEK2 p.Arg148Gly Uncertain significance ★★ ⚠ same residue
- CHEK2 p.Arg148Lys Uncertain significance ★★ same residue
- CHEK2 p.Arg148Thr Uncertain significance ★★ ⚠ same residue
- CHEK2 p.Arg148Ser Uncertain significance ★ ⚠ same residue
- CHEK2 p.Arg148delinsIleAlaLeuMetAsnHisCysTer 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-arg148 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown