Is CDK19 p.Lys83Arg (c.248A>G) pathogenic?

CDK19 p.Lys83Arg (c.248A>G) is classified Uncertain significance in CDK19 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-01). AlphaMissense: likely benign (0.106); Very rare (popmax 0.000509%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CDK19 p.Lys83Arg (c.248A>G)?

CDK19 p.Lys83Arg (c.248A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CDK19 p.Lys83Arg (c.248A>G) in the general population?

CDK19 p.Lys83Arg (c.248A>G) is very rare (popmax 0.000509%, nfe) (gnomAD).

What do computational predictors say about CDK19 p.Lys83Arg (c.248A>G)?

AlphaMissense predicts likely benign (score 0.106) — an in-silico prediction, not a clinical call.

CDK19 p.Lys83Arg

c.248A>G · rs1334230328 · VCV2286861

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.106 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.106	likely benign
REVEL	0.14	moderately benign-leaning
SaProt	LLR -3.06	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 183 kb · p 3.7e-12 · regional, not allelic
Overall
CADD	23.1	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

Grpmax group 0.000509% European (non-Finnish) · 6/1,179,348 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,613,294 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CDK19
Protein: p.Lys83Arg
Coding: c.248A>G
MANE Select: NM_015076
dbSNP: rs1334230328
Type: single nucleotide variant
Location: chr6:110670498 (GRCh38)
Gene constraint: LOEUF 0.655 · pLI 0.49 (gnomAD)
Structure: AlphaFold pLDDT 77.97
Residue 83: 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-lys83arg (accessed [today's date]).

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