Is CDKL5 p.Ser847= (c.2541G>A) pathogenic?

CDKL5 p.Ser847= (c.2541G>A) is classified Benign/Likely benign in CDKL5 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-11). Very rare (popmax 0.00528%, sas); Associated with developmental and epileptic encephalopathy, 2.

What condition is associated with CDKL5 p.Ser847= (c.2541G>A)?

CDKL5 p.Ser847= (c.2541G>A) is associated with developmental and epileptic encephalopathy, 2 (ClinVar).

How common is CDKL5 p.Ser847= (c.2541G>A) in the general population?

CDKL5 p.Ser847= (c.2541G>A) is very rare (popmax 0.00528%, sas) (gnomAD).

How is CDKL5-deficiency disorder inherited?

Typically X-linked dominant (Orphanet). A genetic counselor can assess individual risk for a family.

CDKL5 p.Ser847=

c.2541G>A · rs781774964 · VCV533392

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00528%, sas)

Conditions

developmental and epileptic encephalopathy, 2

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 -0.36	GERP -4.4
Overall
CADD	0.233	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00528% South Asian · 3/56,833 alleles

Filtering AF 0.00207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00181%

Overall 0.00281% 34/1,209,654 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00645%	15,509
South Asiangrpmax	0.00528%	18,944
European (non-Finnish)	0.00302%	33,147
Remaining individualsnot grpmax-eligible	0.0021%	47,583

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser847=
Coding: c.2541G>A
MANE Select: NM_001323289
dbSNP: rs781774964
Type: single nucleotide variant
Location: chrX:18628415 (GRCh38)
Structure: AlphaFold pLDDT 53.76 · 3 PDB
Residue 847: a UniProt-annotated variant site (in dee2)

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

Disease context

developmental and epileptic encephalopathy, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For CDKL5-deficiency disorder (Orphanet):

Inheritance: X-linked dominant
Onset: Infancy, Neonatal

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-ser847 (accessed [today's date]).

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