Is CDKL5 p.Val18Asp (c.53T>A) pathogenic?

CDKL5 p.Val18Asp (c.53T>A) is classified Pathogenic in CDKL5 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-01-27). AlphaMissense: likely pathogenic (0.99); Absent from gnomAD v4.1; Associated with Angelman syndrome-like.

What condition is associated with CDKL5 p.Val18Asp (c.53T>A)?

CDKL5 p.Val18Asp (c.53T>A) is associated with Angelman syndrome-like, developmental and epileptic encephalopathy, 2 (ClinVar).

How common is CDKL5 p.Val18Asp (c.53T>A) in the general population?

CDKL5 p.Val18Asp (c.53T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDKL5 p.Val18Asp (c.53T>A)?

AlphaMissense predicts likely pathogenic (score 0.99) — an in-silico prediction, not a clinical call.

CDKL5 p.Val18Asp

c.53T>A · rs1602230515 · VCV659752

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.99 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Angelman syndrome-like

Computational evidence

Protein change
AlphaMissense	0.99	likely pathogenic ✓ concordant with ClinVar
REVEL	0.58	indeterminate
SaProt	LLR -14.79	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.35	constrained · MANE · 91 kb · p 1.2e-21 · regional, not allelic
Overall
CADD	27.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Val18Asp
Coding: c.53T>A
MANE Select: NM_001323289
dbSNP: rs1602230515
Type: single nucleotide variant
Location: chrX:18507149 (GRCh38)
Structure: AlphaFold pLDDT 53.76 · 3 PDB
Residue 18: the protein kinase domain; a β-strand

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

Disease context

Angelman syndrome-like — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: developmental and epileptic encephalopathy, 2

Similar variants

CDKL5 p.Val18fs Pathogenic ★ 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
CDKL5 p.Arg948Ter 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-val18asp (accessed [today's date]).

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