Is CDKL5 p.Leu67fs (c.200_201del) pathogenic?

CDKL5 p.Leu67fs (c.200201del) is classified Pathogenic in CDKL5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-22). Absent from gnomAD; Associated with CDKL5 disorder.

What condition is associated with CDKL5 p.Leu67fs (c.200_201del)?

CDKL5 p.Leu67fs (c.200_201del) is associated with CDKL5 disorder, developmental and epileptic encephalopathy, 2 (ClinVar).

How common is CDKL5 p.Leu67fs (c.200_201del) in the general population?

CDKL5 p.Leu67fs (c.200_201del) is absent from gnomAD (gnomAD).

CDKL5 p.Leu67fs

c.200_201del · rs1555949011 · VCV533386

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

CDKL5 disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CDKL5
Protein: p.Leu67fs
Coding: c.200_201del
MANE Select: NM_001323289
dbSNP: rs1555949011
Type: Microsatellite
Location: chrX:18575405 (GRCh38)
Structure: AlphaFold pLDDT 53.76 · 3 PDB
Residue 67: the protein kinase domain

Full CDKL5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CDKL5 disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: developmental and epileptic encephalopathy, 2

Similar variants

CDKL5 p.Leu67Phe Uncertain significance ★★★ ⚠ same residue
CDKL5 p.Glu416fs Pathogenic ★★★ same condition
CDKL5 p.Leu405fs Pathogenic ★★★ same condition
CDKL5 p.Cys152_Asp153delinsTer Pathogenic/Likely pathogenic ★★ same condition
CDKL5 p.Glu77fs Pathogenic ★★ same condition
CDKL5 p.His690_Ser691insTer Pathogenic ★★ same condition
CDKL5 p.Lys776fs Pathogenic ★★ same condition
CDKL5 p.Thr169fs 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-leu67fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown