Is CDKL5 p.Glu170Ter (c.508G>T) pathogenic?

CDKL5 p.Glu170Ter (c.508G>T) is classified Pathogenic in CDKL5 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-10-18). Absent from gnomAD v4.1; Associated with developmental and epileptic encephalopathy, 2.

What condition is associated with CDKL5 p.Glu170Ter (c.508G>T)?

CDKL5 p.Glu170Ter (c.508G>T) is associated with developmental and epileptic encephalopathy, 2 (ClinVar).

How common is CDKL5 p.Glu170Ter (c.508G>T) in the general population?

CDKL5 p.Glu170Ter (c.508G>T) is absent from gnomAD v4.1 (gnomAD).

How is CDKL5-deficiency disorder inherited?

Typically X-linked dominant (Orphanet). A genetic counselor can assess individual risk for a family.

CDKL5 p.Glu170Ter

c.508G>T · rs1555950066 · VCV533384

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

Conditions

developmental and epileptic encephalopathy, 2

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 8 of 18
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Overall
CADD	38.0	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.Glu170Ter
Coding: c.508G>T
MANE Select: NM_001323289
dbSNP: rs1555950066
Type: single nucleotide variant
Location: chrX:18584307 (GRCh38)
Structure: AlphaFold pLDDT 53.76 · 3 PDB
Residue 170: the protein kinase domain

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

Disease context

developmental and epileptic encephalopathy, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For CDKL5-deficiency disorder (Orphanet):

Inheritance: X-linked dominant
Onset: Infancy, Neonatal

Similar variants

CDKL5 p.Glu170fs Likely pathogenic ★★ same residue
RS1 p.Thr170Pro Likely pathogenic ★ same residue
RS1 p.Thr170= Likely benign ★ 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

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-glu170ter (accessed [today's date]).

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