CTSC p.Ile424=
c.1272T>A · rs376286500 · VCV2172910
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.01%, amr)
Conditions
3
periodontitis, aggressive
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 0.99 | GERP 0.51, phastCons 0.47 |
| Overall | ||
| CADD | 8.75 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.01%
Admixed American · 6/59,966 alleles
Filtering AF
0.00429%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00295%
Overall
0.000434%
7/1,613,990 alleles · ultra-rare
exomes 7/1,461,846 · genomes 0/152,144 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.01% | 9,994 |
| European (non-Finnish) | 8.47e-05% | 1,180,008 |
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
- CTSC
- Protein
- p.Ile424=
- Coding
- c.1272T>A
- MANE Select
- NM_001814
- dbSNP
- rs376286500
- Type
- single nucleotide variant
- Location
- chr11:88294126 (GRCh38)
- Gene constraint
- LOEUF 1.051 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.64 · 18 PDB
- Residue 424
- a β-strand
Similar variants
- CTSC c.319-1G>A Pathogenic ★★ same condition
- CTSC c.757+1G>T Likely pathogenic ★★ same condition
- CTSC c.-55C>A Pathogenic ★★ same condition
- CTSC p.Arg210Ter Pathogenic ★★ same condition
- CTSC p.Arg250Ter Pathogenic/Likely pathogenic ★★ same condition
- CTSC p.Arg272His Pathogenic/Likely pathogenic ★★ ⚠ same condition
- CTSC p.Arg272Pro Pathogenic/Likely pathogenic ★★ same condition
- CTSC p.Arg339Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
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/ctsc-p-ile424 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown