Is CDKL5 p.Thr803= (c.2409G>A) pathogenic?

CDKL5 p.Thr803= (c.2409G>A) is classified Benign/Likely benign in CDKL5 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-04-20). Rare (popmax 0.31%, afr); Associated with Inborn genetic diseases.

What condition is associated with CDKL5 p.Thr803= (c.2409G>A)?

CDKL5 p.Thr803= (c.2409G>A) is associated with Inborn genetic diseases, developmental and epileptic encephalopathy, 2 (ClinVar).

How common is CDKL5 p.Thr803= (c.2409G>A) in the general population?

CDKL5 p.Thr803= (c.2409G>A) is rare (popmax 0.31%, afr) (gnomAD).

CDKL5 p.Thr803=

c.2409G>A · rs145401225 · VCV136714

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.31%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.23	GERP -5, phastCons 0.001
Overall
CADD	0.246	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.31% African / African-American · 175/56,422 alleles

Filtering AF 0.273% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.258%

Overall 0.0165% 198/1,203,593 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.31%	322
Admixed American	0.0198%	5,042
Remaining individualsnot grpmax-eligible	0.0126%	7,911
South Asian	0.00708%	14,126
Finnishnot grpmax-eligible	0.00439%	22,782
European (non-Finnish)	0.000224%	445,796

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.Thr803=
Coding: c.2409G>A
MANE Select: NM_001323289
dbSNP: rs145401225
Type: single nucleotide variant
Location: chrX:18625160 (GRCh38)
Structure: AlphaFold pLDDT 53.76 · 3 PDB
Residue 803: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: developmental and epileptic encephalopathy, 2

Similar variants

CDKL5 p.Thr803Met 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
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-thr803 (accessed [today's date]).

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