CDKL5 p.Lys84Ter
c.250A>T · rs587783074 · VCV156593
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 5 of 18 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 2.4, phastCons 1 |
| Overall | ||
| CADD | 36.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
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.Lys84Ter
- Coding
- c.250A>T
- MANE Select
- NM_001323289
- dbSNP
- rs587783074
- Type
- single nucleotide variant
- Location
- chrX:18575458 (GRCh38)
- Structure
- AlphaFold pLDDT 53.76 · 3 PDB
- Residue 84
- the protein kinase domain; a β-strand
Similar variants
- RS1 p.Ser84Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
- CDKL5 c.146-1G>A Pathogenic ★★★ same type
- CDKL5 p.Ala157Pro Likely pathogenic ★★★ same type
- CDKL5 p.Ala157Val Likely pathogenic ★★★ same type
- CDKL5 p.Ala40Val Pathogenic ★★★ same type
- CDKL5 p.Arg178Gln Pathogenic ★★★ same type
- CDKL5 p.Arg717= Likely pathogenic ★★★ same type
- CDKL5 p.Arg948Ter Pathogenic ★★★ same type
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-lys84ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown