CTSB p.Ser130=
c.390C>T · rs11548597 · VCV1656261
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.02%, 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 -4.3 | GERP -3.5 |
| Overall | ||
| CADD | 1.305 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.02%
African / African-American · 15/74,928 alleles
Filtering AF
0.0123%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00989%
Overall
0.00248%
40/1,613,442 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.02% | 4,995 |
| Admixed American | 0.01% | 10,000 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,818 |
| South Asian | 0.00439% | 22,765 |
| East Asian | 0.00223% | 44,874 |
| European (non-Finnish) | 0.000932% | 107,260 |
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.Ser130=
- Coding
- c.390C>T
- MANE Select
- NM_001908
- dbSNP
- rs11548597
- Type
- single nucleotide variant
- Location
- chr8:11849102 (GRCh38)
- Gene constraint
- LOEUF 1.756 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 91.95 · 21 PDB
- Residue 130
- a disulfide bond
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-ser130 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown