CTNS p.Ala256=
c.768A>G · rs746564292 · VCV1136445
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0312%, eas)
Conditions
3
Inborn genetic diseases
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 -8.8 | GERP -3.1 |
| Overall | ||
| CADD | 0.08 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0312%
East Asian · 14/44,894 alleles
Filtering AF
0.0188%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0151%
Overall
0.0013%
21/1,612,154 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0312% | 3,207 |
| South Asian | 0.00659% | 15,167 |
| European (non-Finnish) | 8.48e-05% | 1,179,800 |
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
- CTNS
- Protein
- p.Ala256=
- Coding
- c.768A>G
- MANE Select
- NM_004937
- dbSNP
- rs746564292
- Type
- single nucleotide variant
- Location
- chr17:3658091 (GRCh38)
- Gene constraint
- LOEUF 0.754 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 89.27 · 6 PDB
- Residue 256
- an α-helix
Similar variants
- CTNS p.Ala256Leu Uncertain significance ★★ same residue
- CTNS c.140+1G>T Pathogenic/Likely pathogenic ★★ same condition
- CTNS c.140+2T>C Pathogenic/Likely pathogenic ★★ same condition
- CTNS c.141-1G>A Pathogenic/Likely pathogenic ★★ same condition
- CTNS c.141-24T>C Pathogenic ★★ same condition
- CTNS c.225+3A>T Pathogenic/Likely pathogenic ★★ same condition
- CTNS c.225+5G>A Likely pathogenic ★★ same condition
- CTNS c.61+2T>C 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/ctns-p-ala256 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown