CTSK p.Ser209=
c.627T>C · rs746855297 · VCV1089998
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00134%, afr)
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 0.53 | GERP -3.9, phastCons 0.41 |
| Overall | ||
| CADD | 3.132 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00134%
African / African-American · 1/74,838 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000186%
3/1,613,858 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00134% | 74,838 |
| European (non-Finnish) | 0.000169% | 589,995 |
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
- CTSK
- Protein
- p.Ser209=
- Coding
- c.627T>C
- MANE Select
- NM_000396
- dbSNP
- rs746855297
- Type
- single nucleotide variant
- Location
- chr1:150799701 (GRCh38)
- Gene constraint
- LOEUF 0.748 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.89 · 70 PDB
- Residue 209
- an α-helix; a disulfide bond
Similar variants
- CTSK c.121-1G>A Pathogenic/Likely pathogenic ★★ same type
- CTSK c.121-2A>G Pathogenic/Likely pathogenic ★★ same type
- CTSK c.244-29A>G Pathogenic/Likely pathogenic ★★ same type
- CTSK c.244-2A>C Likely pathogenic ★★ same type
- CTSK c.400-1G>C Likely pathogenic ★★ same type
- CTSK c.784+1G>A Likely pathogenic ★★ same type
- CTSK p.Ala277Val Pathogenic ★★ same type
- CTSK p.Arg122Ter Pathogenic/Likely pathogenic ★★ 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/ctsk-p-ser209 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown