CDKL5 p.Ser196=
c.588G>A · rs750492179 · VCV1935188
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00435%, amr)
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 -0.21 | GERP -5, phastCons 0.004 |
| Overall | ||
| CADD | 3.468 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00435%
Admixed American · 2/45,992 alleles
Filtering AF
0.000721%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00027%
Overall
0.000413%
5/1,210,779 alleles · very rare
exomes 5/1,097,371 · genomes 0/113,408 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00435% | 22,996 |
| European (non-Finnish) | 0.000335% | 298,252 |
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.Ser196=
- Coding
- c.588G>A
- MANE Select
- NM_001323289
- dbSNP
- rs750492179
- Type
- single nucleotide variant
- Location
- chrX:18587987 (GRCh38)
- Structure
- AlphaFold pLDDT 53.76 · 3 PDB
- Residue 196
- the protein kinase domain; a UniProt-annotated variant site (in dee2); an α-helix
Similar variants
- CDKL5 p.Ser196Leu Pathogenic/Likely pathogenic ★★ same residue
- RS1 p.Ser196Ala 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
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-ser196 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown