CASK c.532+2T>C
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
canonical splice-site (±1/±2)
predicted LoF
gnomAD v4.1
Not reported
no allele count reported in gnomAD v4.1 (AN 1,120,169)
Conditions
1
Intellectual disability, CASK-related, X-linked
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Consequence | canonical splice-site (±1/±2) | predicted loss-of-function |
|---|---|---|
| Splicing | ||
| Splice region | donor +2 | canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone |
| SpliceAI | Δ0.95 | donor loss · deltas |
| Pangolin | Δ0.83 | loss · gain 0.02 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 1.6, phastCons 1 |
| Non-coding constraint | — | not assessed · autosomes only, so chrX has no window · absence ≠ unconstrained |
| Overall | ||
| CADD | 25.8 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
No allele count reported in gnomAD v4.1 (AN 1,120,169). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.
Variant & gene context
- Gene
- CASK
- Coding
- c.532+2T>C
- MANE Select
- NM_001367721
- dbSNP
- rs2519234356
- Type
- single nucleotide variant
- Location
- chrX:41671426 (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-532-plus-2t-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown