CTSL p.Gly284=
c.852A>C · rs537147424 · VCV753687
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0365%, nfe)
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 -13 | GERP -2.9 |
| Overall | ||
| CADD | 1.506 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0365%
European (non-Finnish) · 431/1,179,730 alleles
Filtering AF
0.0337%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0325%
Overall
0.0286%
461/1,613,398 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0365% | 2,737 |
| Remaining individualsnot grpmax-eligible | 0.0208% | 4,805 |
| Admixed American | 0.0184% | 5,441 |
| African / African-American | 0.008% | 12,498 |
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
- CTSL
- Protein
- p.Gly284=
- Coding
- c.852A>C
- MANE Select
- NM_001912
- dbSNP
- rs537147424
- Type
- single nucleotide variant
- Location
- chr9:87730448 (GRCh38)
- Gene constraint
- LOEUF 0.932 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.75 · 64 PDB
- Residue 284
- a disulfide bond; a β-strand
Similar variants
- CTSL p.Thr207Ile Uncertain significance ★★ ⚠ same type
- CTSL p.Ser117Tyr Benign ★★ ⚠ same type
- CTSL p.Ala143Thr Uncertain significance ★ ⚠ same type
- CTSL p.Ala15Val Uncertain significance ★ ⚠ same type
- CTSL p.Ala220Gly Uncertain significance ★ ⚠ same type
- CTSL p.Ala50Gly Uncertain significance ★ ⚠ same type
- CTSL p.Arg153Gln Uncertain significance ★ ⚠ same type
- CTSL p.Arg153Trp 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/ctsl-p-gly284 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown