CDKL5 p.Val226=
c.678G>A · rs2518857515 · VCV1755431
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00157%, nfe)
Conditions
2
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.27 | donor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 8.5 | GERP 1.6, phastCons 1 |
| Overall | ||
| CADD | 16.04 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00157%
European (non-Finnish) · 14/894,359 alleles
Filtering AF
0.000908%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00071%
Overall
0.00128%
14/1,096,949 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
- CDKL5
- Protein
- p.Val226=
- Coding
- c.678G>A
- MANE Select
- NM_001323289
- dbSNP
- rs2518857515
- Type
- single nucleotide variant
- Location
- chrX:18588077 (GRCh38)
- Structure
- AlphaFold pLDDT 53.76 · 3 PDB
- Residue 226
- the protein kinase domain; an α-helix
Similar variants
- 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
- CDKL5 p.Asp193Gly Likely 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-val226 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown