Is CDK19 p.Ala208Ser (c.622G>T) pathogenic?

CDK19 p.Ala208Ser (c.622G>T) is classified Uncertain significance in CDK19 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-14). AlphaMissense: likely pathogenic (0.6011); Absent from gnomAD v4.1; Associated with developmental and epileptic encephalopathy, 87.

What condition is associated with CDK19 p.Ala208Ser (c.622G>T)?

CDK19 p.Ala208Ser (c.622G>T) is associated with developmental and epileptic encephalopathy, 87 (ClinVar).

How common is CDK19 p.Ala208Ser (c.622G>T) in the general population?

CDK19 p.Ala208Ser (c.622G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDK19 p.Ala208Ser (c.622G>T)?

AlphaMissense predicts likely pathogenic (score 0.6011) — an in-silico prediction, not a clinical call.

CDK19 p.Ala208Ser

c.622G>T · VCV4881242

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6011 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy, 87

Computational evidence

Protein change
AlphaMissense	0.6011	likely pathogenic
REVEL	0.252	benign-leaning
SaProt	LLR -7.07	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.7, phastCons 1
Regional constraint	o/e 0.40	unconstrained · MANE · 9,205 bp · p 7.7e-14 · regional, not allelic
Overall
CADD	27.2	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: CDK19
Protein: p.Ala208Ser
Coding: c.622G>T
MANE Select: NM_015076
Type: single nucleotide variant
Location: chr6:110632054 (GRCh38)
Gene constraint: LOEUF 0.655 · pLI 0.49 (gnomAD)
Structure: AlphaFold pLDDT 77.97
Residue 208: the protein kinase domain

Full CDK19 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

developmental and epileptic encephalopathy, 87 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDK19 p.Thr196Ala Pathogenic/Likely pathogenic ★★ ⚠ same condition
CDK19 p.Trp198Cys Uncertain significance ★★ ⚠ same condition
CDK19 c.457-3T>C Uncertain significance ★ same condition
CDK19 p.Ala214Thr Uncertain significance ★ ⚠ same condition
CDK19 p.Ala412Ser Uncertain significance ★ ⚠ same condition
CDK19 p.Arg323Lys Uncertain significance ★ ⚠ same condition
CDK19 p.Gln424Ter Uncertain significance ★ same condition
CDK19 p.Gly348Ser Uncertain significance ★ ⚠ 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/cdk19-p-ala208ser (accessed [today's date]).

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