Is CDKL3 p.Arg463Ser (c.1389A>T) pathogenic?

CDKL3 p.Arg463Ser (c.1389A>T) is classified Uncertain significance in CDKL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-04). AlphaMissense: ambiguous (0.4018); Absent from gnomAD v4.1.

How common is CDKL3 p.Arg463Ser (c.1389A>T) in the general population?

CDKL3 p.Arg463Ser (c.1389A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDKL3 p.Arg463Ser (c.1389A>T)?

AlphaMissense predicts ambiguous (score 0.4018) — an in-silico prediction, not a clinical call.

CDKL3 p.Arg463Ser

c.1389A>T · rs2481455939 · VCV3141632

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4018 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4018	ambiguous
REVEL	0.153	moderately benign-leaning
SaProt	LLR -6.53	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -1, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 68 kb · p 0.16 · regional, not allelic
Overall
CADD	16.16	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: CDKL3
Protein: p.Arg463Ser
Coding: c.1389A>T
MANE Select: NM_001113575
dbSNP: rs2481455939
Type: single nucleotide variant
Location: chr5:134306678 (GRCh38)
Gene constraint: LOEUF 1.523 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.87 · 1 PDB
Residue 463: the 'disordered' region

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.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-arg463ser (accessed [today's date]).

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