Is CDK19 p.Arg237Leu (c.710G>T) pathogenic?

CDK19 p.Arg237Leu (c.710G>T) is classified Uncertain significance in CDK19 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-03). AlphaMissense: likely pathogenic (0.9941); Absent from gnomAD v4.1.

How common is CDK19 p.Arg237Leu (c.710G>T) in the general population?

CDK19 p.Arg237Leu (c.710G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDK19 p.Arg237Leu (c.710G>T)?

AlphaMissense predicts likely pathogenic (score 0.9941) — an in-silico prediction, not a clinical call.

CDK19 p.Arg237Leu

c.710G>T · VCV3897218

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9941 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9941	likely pathogenic
REVEL	0.586	indeterminate
SaProt	LLR -13.08	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	Δ0.42	acceptor gain · deltas
Pangolin	Δ0.26	gain · loss 0.00 · agrees with SpliceAI · independent
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	35.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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.Arg237Leu
Coding: c.710G>T
MANE Select: NM_015076
Type: single nucleotide variant
Location: chr6:110627082 (GRCh38)
Gene constraint: LOEUF 0.655 · pLI 0.49 (gnomAD)
Structure: AlphaFold pLDDT 77.97
Residue 237: the protein kinase domain

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

Similar variants

CDK19 p.Thr196Ala Pathogenic/Likely pathogenic ★★ ⚠ same type
CDK19 p.Lys47Asn Uncertain significance ★★ ⚠ same type
CDK19 p.Pro495Thr Uncertain significance ★★ ⚠ same type
CDK19 p.Trp198Cys Uncertain significance ★★ ⚠ same type
CDK19 p.Arg200Gln Pathogenic ★ same type
CDK19 p.Arg200Trp Likely pathogenic ★ same type
CDK19 c.1111-4A>G Uncertain significance ★ same type
CDK19 c.456+5G>A Uncertain significance ★ same type

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-arg237leu (accessed [today's date]).

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