CHEK2 p.Phe291=
c.873T>C · rs2517886439 · VCV1764510
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000176%, nfe)
Conditions
2
hereditary neoplastic syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.363 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 3.1 | GERP 1.4, phastCons 1 |
| Overall | ||
| CADD | 11.62 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000176%
European (non-Finnish) · 2/1,136,494 alleles
Filtering AF
2.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000128%
2/1,559,368 alleles · very rare
exomes 2/1,407,014 · genomes 0/152,354 · joint denominator
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.Phe291=
- Coding
- c.873T>C
- MANE Select
- NM_007194
- dbSNP
- rs2517886439
- Type
- single nucleotide variant
- Location
- chr22:28703540 (GRCh38)
- Gene constraint
- LOEUF 1.399 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 77.64 · 38 PDB
- Residue 291
- a β-strand; the protein kinase domain
Similar variants
- CHEK2 p.Phe291Ile Uncertain significance ★★ ⚠ same residue
- CHEK2 p.Phe291Leu Uncertain significance ★ ⚠ same residue
- CHEK2 p.Phe291_Phe292insTer Pathogenic ★★ same residue
- CHEK2 p.Phe291fs 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
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-phe291 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown