Is CDKL5 p.Gln606= (c.1818A>G) pathogenic?

CDKL5 p.Gln606= (c.1818A>G) is classified Benign/Likely benign in CDKL5 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-14). Ultra-rare (popmax 0.0193%, afr); Associated with developmental and epileptic encephalopathy, 2.

What condition is associated with CDKL5 p.Gln606= (c.1818A>G)?

CDKL5 p.Gln606= (c.1818A>G) is associated with developmental and epileptic encephalopathy, 2 (ClinVar).

How common is CDKL5 p.Gln606= (c.1818A>G) in the general population?

CDKL5 p.Gln606= (c.1818A>G) is ultra-rare (popmax 0.0193%, afr) (gnomAD).

How is CDKL5-deficiency disorder inherited?

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

CDKL5 p.Gln606=

c.1818A>G · rs587783154 · VCV156686

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0193%, afr)

Conditions

developmental and epileptic encephalopathy, 2

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 1.6	GERP -1.4, phastCons 1
Overall
CADD	5.521	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0193% African / African-American · 11/57,138 alleles

Filtering AF 0.0108% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00831%

Overall 0.00215% 26/1,210,114 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0193%	5,194
East Asian	0.0178%	5,630
Remaining individualsnot grpmax-eligible	0.0021%	47,595
South Asian	0.00176%	56,819
European (non-Finnish)	0.000782%	127,895

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.Gln606=
Coding: c.1818A>G
MANE Select: NM_001323289
dbSNP: rs587783154
Type: single nucleotide variant
Location: chrX:18604742 (GRCh38)
Structure: AlphaFold pLDDT 53.76 · 3 PDB

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.Gln606Ter 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-gln606 (accessed [today's date]).

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