CASK p.Val743=
c.2229C>G · VCV3341941
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00355%, sas)
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 5 | GERP -1.2, phastCons 1 |
| Overall | ||
| CADD | 7.576 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00355%
South Asian · 2/56,324 alleles
Filtering AF
0.000589%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00022%
Overall
0.000186%
2/1,075,067 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.Val743=
- Coding
- c.2229C>G
- MANE Select
- NM_001367721
- Type
- single nucleotide variant
- Location
- chrX:41534900 (GRCh38)
- Structure
- AlphaFold pLDDT 79.45 · 22 PDB
- Residue 743
- a UniProt-annotated variant site (found in a patient with epilepsy and pontocerebellar hypoplasia; likely pathogenic); the guanylate kinase-like domain; the 'required for interaction with nrxn1 (via c-terminal tail)' region; a β-strand
Similar variants
- CASK p.Val743Leu Benign/Likely benign ★★ 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-val743 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown