Is CDKL5 p.Arg313= (c.939A>G) pathogenic?

CDKL5 p.Arg313= (c.939A>G) is classified Likely benign in CDKL5 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-03-05). Very rare (popmax 0.000447%, nfe); Associated with History of neurodevelopmental disorder.

What condition is associated with CDKL5 p.Arg313= (c.939A>G)?

CDKL5 p.Arg313= (c.939A>G) is associated with History of neurodevelopmental disorder, developmental and epileptic encephalopathy, 2 (ClinVar).

How common is CDKL5 p.Arg313= (c.939A>G) in the general population?

CDKL5 p.Arg313= (c.939A>G) is very rare (popmax 0.000447%, nfe) (gnomAD).

CDKL5 p.Arg313=

c.939A>G · rs370986597 · VCV588149

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000447%, nfe)

Conditions

History of neurodevelopmental disorder

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 3.7	GERP -0.011, phastCons 1
Overall
CADD	9.355	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000447% European (non-Finnish) · 4/894,344 alleles

Filtering AF 0.000105% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.1e-05%

Overall 0.000331% 4/1,209,234 alleles · very rare

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.Arg313=
Coding: c.939A>G
MANE Select: NM_001323289
dbSNP: rs370986597
Type: single nucleotide variant
Location: chrX:18598575 (GRCh38)
Structure: AlphaFold pLDDT 53.76 · 3 PDB
Residue 313: the 'disordered' region

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

Disease context

History of neurodevelopmental disorder — 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-arg313 (accessed [today's date]).

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