CHEK2 p.Phe475=
c.1425T>C · rs1601716189 · VCV819168
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
very rare (popmax 6.93e-05%)
Conditions
2
hereditary neoplastic syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.09 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.59 | GERP -3.3, phastCons 0.89 |
| Overall | ||
| CADD | 7.442 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
6.93e-05%
Overall
6.93e-05%
1/1,443,880 alleles · very rare
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.Phe475=
- Coding
- c.1425T>C
- MANE Select
- NM_007194
- dbSNP
- rs1601716189
- Type
- single nucleotide variant
- Location
- chr22:28694068 (GRCh38)
- Gene constraint
- LOEUF 1.399 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 77.64 · 38 PDB
- Residue 475
- the protein kinase domain
Similar variants
- CHEK2 p.Phe475Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
- CHEK2 p.Phe475Val Uncertain significance ★ ⚠ same residue
- CHEK2 p.Phe475fs 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
- CHEK2 c.1008+2T>G Likely pathogenic ★★ same condition
- CHEK2 c.1009-1G>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-phe475 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown