Is CDKL3 p.His282Arg (c.845A>G) pathogenic?

CDKL3 p.His282Arg (c.845A>G) is classified Uncertain significance in CDKL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-10). AlphaMissense: likely benign (0.0618); Very rare (popmax 0.00173%, amr).

How common is CDKL3 p.His282Arg (c.845A>G) in the general population?

CDKL3 p.His282Arg (c.845A>G) is very rare (popmax 0.00173%, amr) (gnomAD).

What do computational predictors say about CDKL3 p.His282Arg (c.845A>G)?

AlphaMissense predicts likely benign (score 0.0618) — an in-silico prediction, not a clinical call.

CDKL3 p.His282Arg

c.845A>G · VCV3489600

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0618 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00173%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0618	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -4.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.25	GERP -4.8, phastCons 0.99
Regional constraint	o/e 0.95	unconstrained · MANE · 68 kb · p 0.16 · regional, not allelic
Overall
CADD	11.74	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00173% Admixed American · 1/57,824 alleles

Overall 6.91e-05% 1/1,447,880 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: CDKL3
Protein: p.His282Arg
Coding: c.845A>G
MANE Select: NM_001113575
Type: single nucleotide variant
Location: chr5:134312328 (GRCh38)
Gene constraint: LOEUF 1.523 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.87 · 1 PDB
Residue 282: the protein kinase domain

Full CDKL3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDKL3 p.Ala195Thr Uncertain significance ★ ⚠ same type
CDKL3 p.Ala235Ser Uncertain significance ★ ⚠ same type
CDKL3 p.Arg101Gln Uncertain significance ★ ⚠ same type
CDKL3 p.Arg111Pro Uncertain significance ★ ⚠ same type
CDKL3 p.Arg148Gln Uncertain significance ★ ⚠ same type
CDKL3 p.Arg164His Uncertain significance ★ ⚠ same type
CDKL3 p.Arg367Thr Uncertain significance ★ ⚠ same type
CDKL3 p.Arg463Ser Uncertain significance ★ ⚠ 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/cdkl3-p-his282arg (accessed [today's date]).

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