CASK c.356+6T>C
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0675%, afr)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +6 | donor splice region (+6, 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 11 | GERP 2, phastCons 1 |
| Non-coding constraint | — | not assessed · autosomes only, so chrX has no window · absence ≠ unconstrained |
| Overall | ||
| CADD | 21.1 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0675%
African / African-American · 38/56,308 alleles
Filtering AF
0.0505%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0446%
Overall
0.00354%
41/1,157,969 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0675% | 1,482 |
| Remaining individualsnot grpmax-eligible | 0.00436% | 22,937 |
| Admixed American | 0.00219% | 45,639 |
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
- Coding
- c.356+6T>C
- MANE Select
- NM_001367721
- dbSNP
- rs200402760
- Type
- single nucleotide variant
- Location
- chrX:41745518 (GRCh38)
- Structure
- AlphaFold pLDDT 79.45 · 22 PDB
Similar variants
- CASK p.Ala300Thr Uncertain significance ★★ ⚠ same condition
- CASK p.Arg560Trp Uncertain significance ★★ ⚠ same condition
- CASK p.Arg766Trp Uncertain significance ★★ ⚠ same condition
- CASK p.Asn31Ser Uncertain significance ★★ ⚠ same condition
- CASK p.Asp330Gly Uncertain significance ★★ ⚠ same condition
- CASK p.Asp498Gly Uncertain significance ★★ ⚠ same condition
- CASK p.Glu662Asp Uncertain significance ★★ ⚠ same condition
- CASK p.Gly21Asp 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-6t-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown