Is CDK19 p.Arg178Gly (c.532A>G) pathogenic?

CDK19 p.Arg178Gly (c.532A>G) is classified Uncertain significance in CDK19 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-29). AlphaMissense: likely pathogenic (0.9997); Absent from gnomAD v4.1.

How common is CDK19 p.Arg178Gly (c.532A>G) in the general population?

CDK19 p.Arg178Gly (c.532A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDK19 p.Arg178Gly (c.532A>G)?

AlphaMissense predicts likely pathogenic (score 0.9997) — an in-silico prediction, not a clinical call.

CDK19 p.Arg178Gly

c.532A>G · rs2114707169 · VCV1690410

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9997 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9997	likely pathogenic · top 10% in CDK19
REVEL	0.767	pathogenic-leaning
SaProt	LLR -13.08	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.43 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.9	GERP -2.5, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 183 kb · p 3.7e-12 · regional, not allelic
Overall
CADD	31.0	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.Arg178Gly
Coding: c.532A>G
MANE Select: NM_015076
dbSNP: rs2114707169
Type: single nucleotide variant
Location: chr6:110632144 (GRCh38)
Gene constraint: LOEUF 0.655 · pLI 0.49 (gnomAD)
Structure: AlphaFold pLDDT 77.97
Residue 178: 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-arg178gly (accessed [today's date]).

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