CDKL5 p.His687=
c.2061T>C · rs1926471798 · VCV2930500
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0231%, mid)
Conditions
2
Angelman syndrome-like
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 1.9 | GERP 1.3, phastCons 1 |
| Overall | ||
| CADD | 8.001 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0231%
Middle Eastern · 1/4,323 alleles
Overall
9.11e-05%
1/1,098,166 alleles · ultra-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
- CDKL5
- Protein
- p.His687=
- Coding
- c.2061T>C
- MANE Select
- NM_001323289
- dbSNP
- rs1926471798
- Type
- single nucleotide variant
- Location
- chrX:18609479 (GRCh38)
- Structure
- AlphaFold pLDDT 53.76 · 3 PDB
- Residue 687
- the 'disordered' region
Similar variants
- CDKL5 p.His687Arg Uncertain significance ★ ⚠ same residue
- CDKL5 c.146-1G>A Pathogenic ★★★ same condition
- CDKL5 p.Ala157Pro Likely pathogenic ★★★ same condition
- CDKL5 p.Ala157Val Likely pathogenic ★★★ same condition
- CDKL5 p.Ala40Val Pathogenic ★★★ same condition
- CDKL5 p.Arg178Gln Pathogenic ★★★ same condition
- CDKL5 p.Arg717= Likely pathogenic ★★★ same condition
- CDKL5 p.Arg948Ter Pathogenic ★★★ 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/cdkl5-p-his687 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown