Is CDK19 p.Ser244Thr (c.731G>C) pathogenic?

CDK19 p.Ser244Thr (c.731G>C) is classified Uncertain significance in CDK19 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-04). AlphaMissense: ambiguous (0.3543); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CDK19 p.Ser244Thr (c.731G>C)?

CDK19 p.Ser244Thr (c.731G>C) is associated with Inborn genetic diseases (ClinVar).

How common is CDK19 p.Ser244Thr (c.731G>C) in the general population?

CDK19 p.Ser244Thr (c.731G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDK19 p.Ser244Thr (c.731G>C)?

AlphaMissense predicts ambiguous (score 0.3543) — an in-silico prediction, not a clinical call.

CDK19 p.Ser244Thr

c.731G>C · VCV3489466

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3543 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3543	ambiguous
REVEL	0.25	benign-leaning
SaProt	LLR -8.05	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
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	27.3	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.Ser244Thr
Coding: c.731G>C
MANE Select: NM_015076
Type: single nucleotide variant
Location: chr6:110627061 (GRCh38)
Gene constraint: LOEUF 0.655 · pLI 0.49 (gnomAD)
Structure: AlphaFold pLDDT 77.97
Residue 244: the protein kinase domain

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

Similar variants

CDK19 p.Thr196Ala Pathogenic/Likely pathogenic ★★ ⚠ same condition
CDK19 p.Lys47Asn Uncertain significance ★★ ⚠ same condition
CDK19 p.Pro495Thr Uncertain significance ★★ ⚠ same condition
CDK19 p.Arg112Cys Uncertain significance ★ ⚠ same condition
CDK19 p.Arg166Met Uncertain significance ★ ⚠ same condition
CDK19 p.Arg441Gln Uncertain significance ★ ⚠ same condition
CDK19 p.Arg464Cys Uncertain significance ★ ⚠ same condition
CDK19 p.Arg464His 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-ser244thr (accessed [today's date]).

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