Is CDK19 p.Thr196Ala (c.586A>G) pathogenic?

CDK19 p.Thr196Ala (c.586A>G) is classified Pathogenic/Likely pathogenic in CDK19 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-07-13). AlphaMissense: likely pathogenic (0.9998); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CDK19 p.Thr196Ala (c.586A>G)?

CDK19 p.Thr196Ala (c.586A>G) is associated with Inborn genetic diseases, developmental and epileptic encephalopathy, 87 (ClinVar).

How common is CDK19 p.Thr196Ala (c.586A>G) in the general population?

CDK19 p.Thr196Ala (c.586A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDK19 p.Thr196Ala (c.586A>G)?

AlphaMissense predicts likely pathogenic (score 0.9998) — an in-silico prediction, not a clinical call.

CDK19 p.Thr196Ala

c.586A>G · rs1779473650 · VCV929847

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9998 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9998	likely pathogenic ✓ concordant with ClinVar · top 10% in CDK19
REVEL	0.829	moderately pathogenic-leaning
SaProt	LLR -13.09	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.7, phastCons 1
Regional constraint	o/e 0.05	constrained · MANE · 49 bp · p 1.8e-05 · regional, not allelic
Overall
CADD	28.3	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.Thr196Ala
Coding: c.586A>G
MANE Select: NM_015076
dbSNP: rs1779473650
Type: single nucleotide variant
Location: chr6:110632090 (GRCh38)
Gene constraint: LOEUF 0.655 · pLI 0.49 (gnomAD)
Structure: AlphaFold pLDDT 77.97
Residue 196: the protein kinase domain; a UniProt-annotated variant site (in dee87; fails to rescue neurologic phenotypes in a drosophila model system)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: developmental and epileptic encephalopathy, 87

Similar variants

CDK19 p.Lys47Asn Uncertain significance ★★ ⚠ same condition
CDK19 p.Pro495Thr Uncertain significance ★★ ⚠ same condition
CDK19 p.Trp198Cys Uncertain significance ★★ ⚠ same condition
CDK19 c.457-3T>C Uncertain significance ★ same condition
CDK19 p.Ala208Ser Uncertain significance ★ same condition
CDK19 p.Ala214Thr Uncertain significance ★ ⚠ same condition
CDK19 p.Ala412Ser Uncertain significance ★ ⚠ same condition
CDK19 p.Arg112Cys 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-thr196ala (accessed [today's date]).

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