Is CDKL5 p.Val192= (c.576G>A) pathogenic?

CDKL5 p.Val192= (c.576G>A) is classified Likely benign in CDKL5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-22). Very rare (popmax 0.000335%, nfe); Associated with Angelman syndrome-like.

What condition is associated with CDKL5 p.Val192= (c.576G>A)?

CDKL5 p.Val192= (c.576G>A) is associated with Angelman syndrome-like, developmental and epileptic encephalopathy, 2 (ClinVar).

How common is CDKL5 p.Val192= (c.576G>A) in the general population?

CDKL5 p.Val192= (c.576G>A) is very rare (popmax 0.000335%, nfe) (gnomAD).

CDKL5 p.Val192=

c.576G>A · rs1461167746 · VCV1573603

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000335%, nfe)

Conditions

Angelman syndrome-like

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 0.31	GERP -5, phastCons 0.56
Overall
CADD	1.043	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000335% European (non-Finnish) · 3/894,339 alleles

Filtering AF 8.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.5e-05%

Overall 0.000248% 3/1,209,006 alleles · very rare exomes 2/1,097,126 · genomes 1/111,880 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CDKL5
Protein: p.Val192=
Coding: c.576G>A
MANE Select: NM_001323289
dbSNP: rs1461167746
Type: single nucleotide variant
Location: chrX:18587975 (GRCh38)
Structure: AlphaFold pLDDT 53.76 · 3 PDB
Residue 192: the protein kinase domain; an α-helix

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.Val192Met Uncertain significance ★ ⚠ same residue
RS1 p.Pro192Thr Pathogenic ★★ same residue
RS1 p.Pro192Ala Likely pathogenic ★ same residue
RS1 p.Pro192His Pathogenic ★ same residue
RS1 p.Pro192Leu Pathogenic ★ same residue
RS1 p.Pro192= Likely benign ★ same residue
CDKL5 c.146-1G>A Pathogenic ★★★ same condition
CDKL5 p.Ala157Pro Likely 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-val192 (accessed [today's date]).

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