Is CDKL5 p.Asp724Val (c.2171A>T) pathogenic?

CDKL5 p.Asp724Val (c.2171A>T) is classified Uncertain significance in CDKL5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-28). AlphaMissense: likely pathogenic (0.7847); Absent from gnomAD v4.1; Associated with Angelman syndrome-like.

What condition is associated with CDKL5 p.Asp724Val (c.2171A>T)?

CDKL5 p.Asp724Val (c.2171A>T) is associated with Angelman syndrome-like, developmental and epileptic encephalopathy, 2 (ClinVar).

How common is CDKL5 p.Asp724Val (c.2171A>T) in the general population?

CDKL5 p.Asp724Val (c.2171A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDKL5 p.Asp724Val (c.2171A>T)?

AlphaMissense predicts likely pathogenic (score 0.7847) — an in-silico prediction, not a clinical call.

CDKL5 p.Asp724Val

c.2171A>T · rs1926616572 · VCV1004575

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7847 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Angelman syndrome-like

Computational evidence

Protein change
AlphaMissense	0.7847	likely pathogenic
REVEL	0.427	indeterminate
SaProt	LLR -6.25	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 30 kb · p 1.5e-11 · regional, not allelic
Overall
CADD	25.5	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.Asp724Val
Coding: c.2171A>T
MANE Select: NM_001323289
dbSNP: rs1926616572
Type: single nucleotide variant
Location: chrX:18613170 (GRCh38)
Structure: AlphaFold pLDDT 53.76 · 3 PDB
Residue 724: the 'disordered' region

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

Disease context

Angelman syndrome-like — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: developmental and epileptic encephalopathy, 2

Similar variants

CDKL5 p.Asp724Gly Uncertain significance ★ ⚠ same residue
CDKL5 c.146-1G>A Pathogenic ★★★ same condition
CDKL5 p.Ala157Pro Likely pathogenic ★★★ same condition
CDKL5 p.Ala157Val Likely pathogenic ★★★ same condition
CDKL5 p.Ala40Val Pathogenic ★★★ same condition
CDKL5 p.Arg178Gln Pathogenic ★★★ same condition
CDKL5 p.Arg717= Likely pathogenic ★★★ same condition
CDKL5 p.Arg948Ter Pathogenic ★★★ same condition

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-asp724val (accessed [today's date]).

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