Is CDK19 p.Ser496Thr (c.1486T>A) pathogenic?

CDK19 p.Ser496Thr (c.1486T>A) is classified Uncertain significance in CDK19 (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely benign (0.0697); Absent from gnomAD v4.1; Associated with developmental and epileptic encephalopathy, 87.

What condition is associated with CDK19 p.Ser496Thr (c.1486T>A)?

CDK19 p.Ser496Thr (c.1486T>A) is associated with developmental and epileptic encephalopathy, 87 (ClinVar).

How common is CDK19 p.Ser496Thr (c.1486T>A) in the general population?

CDK19 p.Ser496Thr (c.1486T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDK19 p.Ser496Thr (c.1486T>A)?

AlphaMissense predicts likely benign (score 0.0697) — an in-silico prediction, not a clinical call.

CDK19 p.Ser496Thr

c.1486T>A · rs2535238995 · VCV3235030

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0697 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy, 87

Computational evidence

Protein change
AlphaMissense	0.0697	likely benign
REVEL	0.105	moderately benign-leaning
SaProt	LLR -7.77	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 2.8	GERP 1.6, phastCons 0.95
Regional constraint	o/e 0.70	unconstrained · MANE · 8,332 bp · p 5.7e-06 · regional, not allelic
Overall
CADD	18.51	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: CDK19
Protein: p.Ser496Thr
Coding: c.1486T>A
MANE Select: NM_015076
dbSNP: rs2535238995
Type: single nucleotide variant
Location: chr6:110614558 (GRCh38)
Gene constraint: LOEUF 0.655 · pLI 0.49 (gnomAD)
Structure: AlphaFold pLDDT 77.97
Residue 496: the 'disordered' region

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.Ala208Ser 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

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-ser496thr (accessed [today's date]).

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