CASK p.Leu295=
c.885G>A · rs2519079450 · VCV3036853
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000227%, nfe)
Conditions
1
CASK-related disorder
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 4.8 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 12.43 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000227%
European (non-Finnish) · 2/882,985 alleles
Filtering AF
3.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.4e-05%
Overall
0.000184%
2/1,084,308 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.Leu295=
- Coding
- c.885G>A
- MANE Select
- NM_001367721
- dbSNP
- rs2519079450
- Type
- single nucleotide variant
- Location
- chrX:41636608 (GRCh38)
- Structure
- AlphaFold pLDDT 79.45 · 22 PDB
- Residue 295
- a UniProt-annotated variant site (found in a patient with epilepsy and pontocerebellar hypoplasia; likely pathogenic); an α-helix
Disease context
CASK-related disorder
Similar variants
- GPR34 p.Asn295Ser Benign/Likely benign ★★ same residue
- CASK p.Arg28Ter Pathogenic ★★ same condition
- CASK p.Arg489Trp Pathogenic/Likely pathogenic ★★ same condition
- CASK p.Gln494Ter Pathogenic/Likely pathogenic ★★ same condition
- CASK c.1668+5G>A Likely pathogenic ★ same condition
- CASK c.1737+2T>A Pathogenic ★ same condition
- CASK c.708+2T>G Pathogenic ★ same condition
- CASK c.709-1G>A 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/cask-p-leu295 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown