CASK p.Lys715Arg
c.2144A>G · VCV3368702
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.4423 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/2 damaging
REVEL, SaProt · AlphaMissense no call
Computational evidence
| Protein change | ||
| AlphaMissense | 0.4423 | ambiguous |
|---|---|---|
| REVEL | 0.722 | pathogenic-leaning |
| SaProt | LLR -10.14 | damaging |
| ⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.9 | GERP 1.9, phastCons 1 |
| Regional constraint | o/e 0.70 | unconstrained · MANE · 22 kb · p 7.7e-05 · regional, not allelic |
| Overall | ||
| CADD | 26.8 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
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
- Protein
- p.Lys715Arg
- Coding
- c.2144A>G
- MANE Select
- NM_001367721
- Type
- single nucleotide variant
- Location
- chrX:41542702 (GRCh38)
- Structure
- AlphaFold pLDDT 79.45 · 22 PDB
- Residue 715
- a UniProt-annotated variant site (found in a patient with epilepsy and pontocerebellar hypoplasia; likely pathogenic); the 'required for interaction with nrxn1 (via c-terminal tail)' region
Similar variants
- 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
- CASK p.Arg255Cys Pathogenic/Likely 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-lys715arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown