CDKL5 p.Pro823=
c.2469C>T · rs369377144 · VCV287145
ClinGen expert panel — Rett and Angelman-like Disorders VCEP
Benign for CDKL5 disorder. Applied ACMG criteria (verbatim):
BS2 BS1 BP7
Curation rationale (ClinGen, verbatim)
The allele frequency of the p.Pro823= variant in CDKL5 is 0.0088% in African/African American sub population in gnomAD v4, which is high enough to meet the BS1 criteria based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BS1). The p.Pro823= variant is observed in at least 2 unaffected individuals (GeneDX internal database) (BS2). The silent p.Pro823= variant is not predicted to affect splicing using multiple computational tools and does not affect a highly conserved nucleotide (BP7). In summary, the p.Pro823= variant in CDKL5 is classified as benign based on the ACMG/AMP criteria (BS1, BS2, BP7).
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.66 | GERP -5, phastCons 0.045 |
| Overall | ||
| CADD | 0.952 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00885% | 11,296 |
| Admixed American | 0.0022% | 45,370 |
| European (non-Finnish) | 0.00213% | 47,047 |
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.Pro823=
- Coding
- c.2469C>T
- MANE Select
- NM_001323289
- dbSNP
- rs369377144
- Type
- single nucleotide variant
- Location
- chrX:18625220 (GRCh38)
- Structure
- AlphaFold pLDDT 53.76 · 3 PDB
- Residue 823
- the 'disordered' region; a UniProt-annotated variant site (in dee2)
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.Asn71Asp 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-pro823 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown