Is CDKL5 p.Asp135= (c.405T>C) pathogenic?

CDKL5 p.Asp135= (c.405T>C) is classified Likely benign in CDKL5 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-07-17). Absent from gnomAD v4.1; Associated with CDKL5 disorder.

What condition is associated with CDKL5 p.Asp135= (c.405T>C)?

CDKL5 p.Asp135= (c.405T>C) is associated with CDKL5 disorder (ClinVar).

How common is CDKL5 p.Asp135= (c.405T>C) in the general population?

CDKL5 p.Asp135= (c.405T>C) is absent from gnomAD v4.1 (gnomAD).

CDKL5 p.Asp135=

c.405T>C · rs786204957 · VCV189538

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,185,688)

Conditions

CDKL5 disorder

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 5	GERP 1.3, phastCons 1
Overall
CADD	14.52	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,185,688). 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.Asp135=
Coding: c.405T>C
MANE Select: NM_001323289
dbSNP: rs786204957
Type: single nucleotide variant
Location: chrX:18581892 (GRCh38)
Structure: AlphaFold pLDDT 53.76 · 3 PDB
Residue 135: the protein kinase domain; an active site

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

Similar variants

CDKL5 p.Asp135Gly Uncertain significance ★ ⚠ same residue
CDKL5 p.Asp135Val Uncertain significance ★★ ⚠ same residue
CDKL5 p.Asp135His Likely pathogenic ★ same residue
RS1 p.Gly135Glu Pathogenic ★ same residue
CDKL5 p.Asp135Glu Uncertain significance ★ ⚠ same residue
RS1 p.Gly135Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
RS1 p.Gly135Arg Uncertain significance ★ ⚠ same residue
CDKL5 c.146-1G>A 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-asp135 (accessed [today's date]).

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