CASK c.356+4T>A
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
Intellectual disability, CASK-related, X-linked
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +4 | donor splice region (+4, within the first 6 intronic nt) · inside the BP7-excluded zone |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.93 | GERP 0.81, phastCons 0.9 |
| Non-coding constraint | — | not assessed · autosomes only, so chrX has no window · absence ≠ unconstrained |
| Overall | ||
| CADD | 14.39 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- CASK
- Coding
- c.356+4T>A
- MANE Select
- NM_001367721
- dbSNP
- rs2147736000
- Type
- single nucleotide variant
- Location
- chrX:41745520 (GRCh38)
- Structure
- AlphaFold pLDDT 79.45 · 22 PDB
Similar variants
- CASK p.Arg489Gln Pathogenic/Likely pathogenic ★★ same condition
- CASK p.Ala359Val Uncertain significance ★★ ⚠ same condition
- CASK p.Ala833Thr Uncertain significance ★★ ⚠ same condition
- CASK p.Arg130Cys Uncertain significance ★★ ⚠ same condition
- CASK p.Arg572His Uncertain significance ★★ ⚠ same condition
- CASK p.Arg61Trp Uncertain significance ★★ ⚠ same condition
- CASK p.Asp424Gly Uncertain significance ★★ ⚠ same condition
- CASK p.Asp445Asn Uncertain significance ★★ ⚠ 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-c-356-plus-4t-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown