CTSC p.Glu447=
c.1341G>A · rs1214651337 · VCV2939922
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, 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 0.4 | GERP 0.87, phastCons 0.99 |
| Overall | ||
| CADD | 7.369 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/59,998 alleles
Overall
0.000137%
2/1,461,852 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 59,998 |
| European (non-Finnish) | 8.47e-05% | 1,180,018 |
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.Glu447=
- Coding
- c.1341G>A
- MANE Select
- NM_001814
- dbSNP
- rs1214651337
- Type
- single nucleotide variant
- Location
- chr11:88294057 (GRCh38)
- Gene constraint
- LOEUF 1.051 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.64 · 18 PDB
- Residue 447
- a UniProt-annotated variant site (in pls); an α-helix
Similar variants
- CTSC p.Glu447Ter Likely pathogenic ★★ same residue
- 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
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-glu447 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown