Is CDKL5 p.Arg752= (c.2256A>G) pathogenic?

CDKL5 p.Arg752= (c.2256A>G) is classified Benign in CDKL5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-22). Ultra-rare (popmax 0.0849%, sas); Associated with Angelman syndrome-like.

What condition is associated with CDKL5 p.Arg752= (c.2256A>G)?

CDKL5 p.Arg752= (c.2256A>G) is associated with Angelman syndrome-like, developmental and epileptic encephalopathy, 2 (ClinVar).

How common is CDKL5 p.Arg752= (c.2256A>G) in the general population?

CDKL5 p.Arg752= (c.2256A>G) is ultra-rare (popmax 0.0849%, sas) (gnomAD).

CDKL5 p.Arg752=

c.2256A>G · rs770193102 · VCV1165618

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0849%, sas)

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 7	GERP 2.1, phastCons 1
Overall
CADD	11.23	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0849% South Asian · 48/56,566 alleles

Filtering AF 0.0657% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0589%

Overall 0.00433% 52/1,201,821 alleles · ultra-rare exomes 50/1,090,552 · genomes 2/111,269 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0849%	1,178
Remaining individualsnot grpmax-eligible	0.00636%	15,717
European (non-Finnish)	0.000112%	890,092

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.Arg752=
Coding: c.2256A>G
MANE Select: NM_001323289
dbSNP: rs770193102
Type: single nucleotide variant
Location: chrX:18613255 (GRCh38)
Structure: AlphaFold pLDDT 53.76 · 3 PDB
Residue 752: 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 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
CDKL5 p.Asp193Gly 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-arg752 (accessed [today's date]).

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