CILK1 p.Ser17=
c.51C>T · rs373305658 · VCV1680573
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0986%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.9 | GERP -2, phastCons 1 |
| Overall | ||
| CADD | 9.613 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0986%
Middle Eastern · 6/6,084 alleles
Filtering AF
0.0429%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0375%
Overall
0.0137%
221/1,613,846 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0986% | 1,014 |
| South Asian | 0.0538% | 1,859 |
| Remaining individualsnot grpmax-eligible | 0.0176% | 5,680 |
| European (non-Finnish) | 0.0125% | 7,972 |
| African / African-American | 0.00534% | 18,724 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,600 |
| East Asian | 0.00223% | 44,898 |
| Admixed American | 0.00167% | 60,000 |
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
- CILK1
- Protein
- p.Ser17=
- Coding
- c.51C>T
- MANE Select
- NM_014920
- dbSNP
- rs373305658
- Type
- single nucleotide variant
- Location
- chr6:53041186 (GRCh38)
- Gene constraint
- LOEUF 0.774 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 61.47
- Residue 17
- the protein kinase domain; a binding site
Similar variants
- CILK1 p.Ser17Phe Uncertain significance ★★ ⚠ same residue
- CILK1 c.1344-4T>A Uncertain significance ★★ same type
- CILK1 p.Ala629Thr Uncertain significance ★★ ⚠ same type
- CILK1 p.Arg124Gln Uncertain significance ★★ ⚠ same type
- CILK1 p.Arg151Gln Uncertain significance ★★ ⚠ same type
- CILK1 p.Arg262Lys Uncertain significance ★★ ⚠ same type
- CILK1 p.Arg280Gln Uncertain significance ★★ ⚠ same type
- CILK1 p.Arg332Gln Uncertain significance ★★ ⚠ same type
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/cilk1-p-ser17 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown