Is CDKL5 p.Arg822= (c.2466C>G) pathogenic?

CDKL5 p.Arg822= (c.2466C>G) is classified Benign/Likely benign in CDKL5 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-28). Rare (popmax 0.248%, afr); Associated with Angelman syndrome-like.

What condition is associated with CDKL5 p.Arg822= (c.2466C>G)?

CDKL5 p.Arg822= (c.2466C>G) is associated with Angelman syndrome-like, developmental and epileptic encephalopathy, 2 (ClinVar).

How common is CDKL5 p.Arg822= (c.2466C>G) in the general population?

CDKL5 p.Arg822= (c.2466C>G) is rare (popmax 0.248%, afr) (gnomAD).

CDKL5 p.Arg822=

c.2466C>G · rs146488512 · VCV258979

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.248%, afr)

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 -0.18	GERP -5, phastCons 0.37
Overall
CADD	1.308	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.248% African / African-American · 140/56,559 alleles

Filtering AF 0.214% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.201%

Overall 0.0121% 146/1,206,133 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.248%	404
Admixed American	0.00661%	15,138
Remaining individualsnot grpmax-eligible	0.00631%	15,845

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.Arg822=
Coding: c.2466C>G
MANE Select: NM_001323289
dbSNP: rs146488512
Type: single nucleotide variant
Location: chrX:18625217 (GRCh38)
Structure: AlphaFold pLDDT 53.76 · 3 PDB
Residue 822: the 'disordered' region; a UniProt-annotated variant site (in dee2)

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.Arg822His Likely benign ★★★ same residue
CDKL5 p.Arg822Cys Uncertain significance ★★ ⚠ same residue
CDKL5 p.Arg822fs 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-arg822 (accessed [today's date]).

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