CASK p.Ala2=
c.6C>G · VCV4084907
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000112%, 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 6.3 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 13.19 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000112%
European (non-Finnish) · 1/894,751 alleles
Overall
9.11e-05%
1/1,097,540 alleles · very rare
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
- CASK
- Protein
- p.Ala2=
- Coding
- c.6C>G
- MANE Select
- NM_001367721
- Type
- single nucleotide variant
- Location
- chrX:41922983 (GRCh38)
- Structure
- AlphaFold pLDDT 79.45 · 22 PDB
- Residue 2
- an α-helix
Similar variants
- CASK p.Ala2Thr Uncertain significance ★ ⚠ same residue
- CASK c.1015+1G>A Pathogenic ★★ same type
- CASK c.1315-1G>A Pathogenic/Likely pathogenic ★★ same type
- CASK c.2317+1G>A Pathogenic/Likely pathogenic ★★ same type
- CASK c.2317+5G>A Pathogenic/Likely pathogenic ★★ same type
- CASK c.2521-2A>G Pathogenic/Likely pathogenic ★★ same type
- CASK c.59+2T>C Pathogenic/Likely pathogenic ★★ same type
- CASK p.Arg106Ter Pathogenic ★★ 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/cask-p-ala2 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown