Is CDKL5 p.Arg444= (c.1332C>T) pathogenic?

CDKL5 p.Arg444= (c.1332C>T) is classified Benign/Likely benign in CDKL5 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-03). Rare (popmax 0.656%, afr); Associated with History of neurodevelopmental disorder.

What condition is associated with CDKL5 p.Arg444= (c.1332C>T)?

CDKL5 p.Arg444= (c.1332C>T) is associated with History of neurodevelopmental disorder, developmental and epileptic encephalopathy, 2 (ClinVar).

How common is CDKL5 p.Arg444= (c.1332C>T) in the general population?

CDKL5 p.Arg444= (c.1332C>T) is rare (popmax 0.656%, afr) (gnomAD).

CDKL5 p.Arg444=

c.1332C>T · rs150844616 · VCV136711

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

rare (popmax 0.656%, afr)

Conditions

History of neurodevelopmental 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 -0.77	GERP -4.8
Overall
CADD	3.43	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.656% African / African-American · 376/57,282 alleles

Filtering AF 0.602% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.58%

Overall 0.039% 472/1,210,299 alleles · rare exomes 268/1,098,173 · genomes 204/112,126 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.656%	152
Middle Eastern	0.138%	725
Admixed American	0.072%	1,388
Remaining individualsnot grpmax-eligible	0.0525%	1,905
South Asian	0.00704%	14,209
European (non-Finnish)	0.00313%	31,975

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.Arg444=
Coding: c.1332C>T
MANE Select: NM_001323289
dbSNP: rs150844616
Type: single nucleotide variant
Location: chrX:18604256 (GRCh38)
Structure: AlphaFold pLDDT 53.76 · 3 PDB
Residue 444: the 'disordered' region; a UniProt-annotated variant site (in)

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

Disease context

History of neurodevelopmental disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: developmental and epileptic encephalopathy, 2

Similar variants

CDKL5 p.Arg444Cys Benign/Likely benign ★★ same residue
CDKL5 p.Arg444His Benign ★ ⚠ same residue
CDKL5 p.Arg444fs 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

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-arg444 (accessed [today's date]).

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