Is CDKL5 p.Ala78= (c.234A>G) pathogenic?

CDKL5 p.Ala78= (c.234A>G) is classified Likely benign in CDKL5 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-11-16). Very rare (popmax 0.0035%, afr); Associated with Angelman syndrome-like.

What condition is associated with CDKL5 p.Ala78= (c.234A>G)?

CDKL5 p.Ala78= (c.234A>G) is associated with Angelman syndrome-like, developmental and epileptic encephalopathy, 2 (ClinVar).

How common is CDKL5 p.Ala78= (c.234A>G) in the general population?

CDKL5 p.Ala78= (c.234A>G) is very rare (popmax 0.0035%, afr) (gnomAD).

CDKL5 p.Ala78=

c.234A>G · rs1288226865 · VCV1158321

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0035%, 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 0.011	GERP -2.2, phastCons 0.8
Overall
CADD	9.086	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0035% African / African-American · 2/57,214 alleles

Filtering AF 0.00058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000217%

Overall 0.000248% 3/1,208,493 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0035%	28,607
European (non-Finnish)	0.000112%	893,791

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.Ala78=
Coding: c.234A>G
MANE Select: NM_001323289
dbSNP: rs1288226865
Type: single nucleotide variant
Location: chrX:18575442 (GRCh38)
Structure: AlphaFold pLDDT 53.76 · 3 PDB
Residue 78: the protein kinase domain; a β-strand

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

RS1 p.Pro78Leu Uncertain significance ★★ ⚠ same residue
RS1 p.Pro78= Conflicting classifications of pathogenicity ★ 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

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-ala78 (accessed [today's date]).

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