Is CDKL2 p.Asp327Val (c.980A>T) pathogenic?

CDKL2 p.Asp327Val (c.980A>T) is classified Uncertain significance in CDKL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-04). AlphaMissense: likely benign (0.0867); Absent from gnomAD v4.1.

How common is CDKL2 p.Asp327Val (c.980A>T) in the general population?

CDKL2 p.Asp327Val (c.980A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDKL2 p.Asp327Val (c.980A>T)?

AlphaMissense predicts likely benign (score 0.0867) — an in-silico prediction, not a clinical call.

CDKL2 p.Asp327Val

c.980A>T · rs200524804 · VCV3141629

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0867 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0867	likely benign
REVEL	0.264	benign-leaning
SaProt	LLR -5.96	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 3.9	GERP 0.79, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 44 kb · p 0.64 · regional, not allelic
Overall
CADD	23.5	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

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: CDKL2
Protein: p.Asp327Val
Coding: c.980A>T
MANE Select: NM_001330724
dbSNP: rs200524804
Type: single nucleotide variant
Location: chr4:75598117 (GRCh38)
Gene constraint: LOEUF 1.223 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.38 · 3 PDB

Full CDKL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDKL2 p.Met215Leu Likely pathogenic ★ ⚠ same type
CDKL2 p.Ala148Gly Uncertain significance ★ ⚠ same type
CDKL2 p.Ala153Thr Uncertain significance ★ ⚠ same type
CDKL2 p.Ala279Asp Uncertain significance ★ ⚠ same type
CDKL2 p.Ala423Ser Uncertain significance ★ ⚠ same type
CDKL2 p.Arg149Gln Uncertain significance ★ ⚠ same type
CDKL2 p.Arg168Thr Uncertain significance ★ ⚠ same type
CDKL2 p.Arg252Cys 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/cdkl2-p-asp327val (accessed [today's date]).

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