CDKL5 p.Asp193His
c.577G>C · VCV3344019
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.9999 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
3/3 damaging
AlphaMissense, REVEL, SaProt
Conditions
1
CDKL5 disorder
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9999 | likely pathogenic ✓ concordant with ClinVar · top 4% in CDKL5 |
|---|---|---|
| REVEL | 0.798 | moderately pathogenic-leaning |
| SaProt | LLR -15.57 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 2.5, phastCons 1 |
| Regional constraint | o/e 0.35 | constrained · MANE · 91 kb · p 1.2e-21 · regional, not allelic |
| Overall | ||
| CADD | 29.5 | 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
- CDKL5
- Protein
- p.Asp193His
- Coding
- c.577G>C
- MANE Select
- NM_001323289
- Type
- single nucleotide variant
- Location
- chrX:18587976 (GRCh38)
- Structure
- AlphaFold pLDDT 53.76 · 3 PDB
- Residue 193
- the protein kinase domain; an α-helix
Similar variants
- CDKL5 p.Asp193Gly Likely pathogenic ★★★ same residue
- CDKL5 p.Asp193Val Likely pathogenic ★★★ same residue
- RS1 p.Pro193Leu Pathogenic ★★ same residue
- RS1 p.Pro193Ser Pathogenic/Likely pathogenic ★★ same residue
- CDKL5 p.Asp193Ala Pathogenic ★ same residue
- CDKL5 p.Asp193Asn Pathogenic ★ same residue
- RS1 p.Pro193His Likely pathogenic ★ same residue
- CDKL5 c.146-1G>A 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-asp193his (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown