CTSH p.His179=
c.537C>T · VCV3498460
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.033%, 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 -6.1 | GERP -4.1 |
| Overall | ||
| CADD | 0.603 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.033%
Middle Eastern · 2/6,062 alleles
Filtering AF
0.00582%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00242%
Overall
0.00105%
17/1,614,216 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.033% | 3,031 |
| Admixed American | 0.00666% | 15,008 |
| African / African-American | 0.00133% | 75,048 |
| European (non-Finnish) | 0.000847% | 118,004 |
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
- CTSH
- Protein
- p.His179=
- Coding
- c.537C>T
- MANE Select
- NM_004390
- Type
- single nucleotide variant
- Location
- chr15:78931462 (GRCh38)
- Gene constraint
- LOEUF 1.267 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.30 · 2 PDB
- Residue 179
- a disulfide bond; a UniProt-annotated variant site (in)
Similar variants
- CTSH p.Ala23Thr Benign ★★ same type
- CTSH p.Gly11= Benign ★★ same type
- CTSH p.Thr48= Benign ★★ same type
- CTSH p.Ala10Val Uncertain significance ★ ⚠ same type
- CTSH p.Ala149Ser Uncertain significance ★ ⚠ same type
- CTSH p.Ala155Thr Uncertain significance ★ ⚠ same type
- CTSH p.Ala165Val Uncertain significance ★ ⚠ same type
- CTSH p.Ala23Val 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/ctsh-p-his179 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown