Is CDKL5 p.Lys150Arg (c.449A>G) pathogenic?

CDKL5 p.Lys150Arg (c.449A>G) is classified Pathogenic in CDKL5 (ClinVar, Single submitter, 1 submitter; last evaluated 2013-06-06). AlphaMissense: ambiguous (0.4954); Absent from gnomAD v4.1.

How common is CDKL5 p.Lys150Arg (c.449A>G) in the general population?

CDKL5 p.Lys150Arg (c.449A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDKL5 p.Lys150Arg (c.449A>G)?

AlphaMissense predicts ambiguous (score 0.4954) — an in-silico prediction, not a clinical call.

CDKL5 p.Lys150Arg

c.449A>G · rs587783083 · VCV156602

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4954 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4954	ambiguous
REVEL	0.618	indeterminate
SaProt	LLR -11.42	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 0.35	constrained · MANE · 91 kb · p 1.2e-21 · regional, not allelic
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDKL5
Protein: p.Lys150Arg
Coding: c.449A>G
MANE Select: NM_001323289
dbSNP: rs587783083
Type: single nucleotide variant
Location: chrX:18581936 (GRCh38)
Structure: AlphaFold pLDDT 53.76 · 3 PDB
Residue 150: the protein kinase domain; a β-strand

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

Similar variants

RS1 p.Lys150Asn Uncertain significance ★★ ⚠ same residue
RS1 p.Lys150Thr Likely pathogenic same residue
CDKL5 p.Lys150fs Pathogenic ★ same residue
CDKL5 c.146-1G>A Pathogenic ★★★ same type
CDKL5 p.Ala157Pro Likely pathogenic ★★★ same type
CDKL5 p.Ala157Val Likely pathogenic ★★★ same type
CDKL5 p.Ala40Val Pathogenic ★★★ same type
CDKL5 p.Arg178Gln Pathogenic ★★★ same type

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-lys150arg (accessed [today's date]).

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