Is CDKL3 p.Arg148Gln (c.443G>A) pathogenic?

CDKL3 p.Arg148Gln (c.443G>A) is classified Uncertain significance in CDKL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-25). AlphaMissense: likely pathogenic (0.9194); Very rare (popmax 0.00904%, eas).

How common is CDKL3 p.Arg148Gln (c.443G>A) in the general population?

CDKL3 p.Arg148Gln (c.443G>A) is very rare (popmax 0.00904%, eas) (gnomAD).

What do computational predictors say about CDKL3 p.Arg148Gln (c.443G>A)?

AlphaMissense predicts likely pathogenic (score 0.9194) — an in-silico prediction, not a clinical call.

CDKL3 p.Arg148Gln

c.443G>A · rs1752952325 · VCV3141635

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9194 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00904%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9194	likely pathogenic
REVEL	0.635	indeterminate
SaProt	LLR -13.74	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 68 kb · p 0.16 · regional, not allelic
Overall
CADD	29.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00904% East Asian · 4/44,226 alleles

Filtering AF 0.00301% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00182%

Overall 0.000629% 10/1,589,684 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00904%	11,057
European (non-Finnish)	0.000514%	194,588

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.Arg148Gln
Coding: c.443G>A
MANE Select: NM_001113575
dbSNP: rs1752952325
Type: single nucleotide variant
Location: chr5:134350345 (GRCh38)
Gene constraint: LOEUF 1.523 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.87 · 1 PDB
Residue 148: 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.Arg164His Uncertain significance ★ ⚠ same type
CDKL3 p.Arg367Thr Uncertain significance ★ ⚠ same type
CDKL3 p.Arg463Ser Uncertain significance ★ ⚠ same type
CDKL3 p.Arg464Cys 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-arg148gln (accessed [today's date]).

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