CASK p.Arg560=
c.1680G>A · rs1175609035 · VCV1777907
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000224%, nfe)
Conditions
1
Inborn genetic diseases
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 0.39 | GERP -2, phastCons 0.99 |
| Overall | ||
| CADD | 7.477 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000224%
European (non-Finnish) · 2/891,572 alleles
Filtering AF
3.7e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.4e-05%
Overall
0.000166%
2/1,205,969 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.Arg560=
- Coding
- c.1680G>A
- MANE Select
- NM_001367721
- dbSNP
- rs1175609035
- Type
- single nucleotide variant
- Location
- chrX:41559836 (GRCh38)
- Structure
- AlphaFold pLDDT 79.45 · 22 PDB
- Residue 560
- a UniProt-annotated variant site (found in a patient with epilepsy and pontocerebellar hypoplasia; likely pathogenic); the pdz domain; the 'required for interaction with nrxn1 (via c-terminal tail)' region
Similar variants
- CASK p.Arg560Trp Uncertain significance ★★ ⚠ same residue
- CASK p.Ala300Thr 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-p-arg560 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown