Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.53%, 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 3.3 | GERP -0.41, phastCons 1 |
| Overall | ||
| CADD | 10.1 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.53%
African / African-American · 1,872/73,960 alleles
Filtering AF
2.44%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.4%
Overall
0.155%
2,477/1,599,910 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.53% | 40 |
| Admixed American | 0.289% | 346 |
| Remaining individualsnot grpmax-eligible | 0.168% | 595 |
| Middle Eastern | 0.0834% | 1,199 |
| European (non-Finnish) | 0.0277% | 3,607 |
| South Asian | 0.0135% | 7,420 |
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
- CTSB
- Protein
- p.Ser194=
- Coding
- c.582C>T
- MANE Select
- NM_001908
- dbSNP
- rs2230070
- Type
- single nucleotide variant
- Location
- chr8:11847773 (GRCh38)
- Gene constraint
- LOEUF 1.756 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 91.95 · 21 PDB
- Residue 194
- a disulfide bond; a β-strand
Similar variants
- CTSB p.Arg331Pro Uncertain significance ★★ ⚠ same type
- CTSB p.Asp333Asn Uncertain significance ★★ ⚠ same type
- CTSB p.Lys220Glu Uncertain significance ★★ ⚠ same type
- CTSB p.Met73Thr Uncertain significance ★★ ⚠ same type
- CTSB p.Thr332Ala Uncertain significance ★★ ⚠ same type
- CTSB c.327+20C>T Benign ★★ same type
- CTSB c.446+9G>C Benign ★★ same type
- CTSB c.447-16G>C Benign ★★ 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/ctsb-p-ser194 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown