Is CDK19 p.Met297Val (c.889A>G) pathogenic?

CDK19 p.Met297Val (c.889A>G) is classified Uncertain significance in CDK19 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-22). AlphaMissense: ambiguous (0.552); Very rare (popmax 8.48e-05%, nfe).

How common is CDK19 p.Met297Val (c.889A>G) in the general population?

CDK19 p.Met297Val (c.889A>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CDK19 p.Met297Val (c.889A>G)?

AlphaMissense predicts ambiguous (score 0.552) — an in-silico prediction, not a clinical call.

CDK19 p.Met297Val

c.889A>G · rs777727767 · VCV1393897

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.552 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.552	ambiguous
REVEL	0.232	benign-leaning
SaProt	LLR -12.26	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.6, phastCons 1
Regional constraint	o/e 0.40	unconstrained · MANE · 9,205 bp · p 7.7e-14 · regional, not allelic
Overall
CADD	25.6	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

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,910 alleles

Overall 6.84e-05% 1/1,461,702 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.Met297Val
Coding: c.889A>G
MANE Select: NM_015076
dbSNP: rs777727767
Type: single nucleotide variant
Location: chr6:110623334 (GRCh38)
Gene constraint: LOEUF 0.655 · pLI 0.49 (gnomAD)
Structure: AlphaFold pLDDT 77.97
Residue 297: 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-met297val (accessed [today's date]).

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