Is CDK9 p.Val129Met (c.385G>A) pathogenic?

CDK9 p.Val129Met (c.385G>A) is classified Uncertain significance in CDK9 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-07). AlphaMissense: likely pathogenic (0.802); Absent from gnomAD v4.1.

How common is CDK9 p.Val129Met (c.385G>A) in the general population?

CDK9 p.Val129Met (c.385G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDK9 p.Val129Met (c.385G>A)?

AlphaMissense predicts likely pathogenic (score 0.802) — an in-silico prediction, not a clinical call.

CDK9 p.Val129Met

c.385G>A · rs2539003090 · VCV2323201

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.802 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.802	likely pathogenic
REVEL	0.355	indeterminate
SaProt	LLR -6.45	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.6, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 3,391 bp · p 2.2e-09 · regional, not allelic
Overall
CADD	22.8	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: CDK9
Protein: p.Val129Met
Coding: c.385G>A
MANE Select: NM_001261
dbSNP: rs2539003090
Type: single nucleotide variant
Location: chr9:127788066 (GRCh38)
Gene constraint: LOEUF 1.139 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 28 PDB
Residue 129: the protein kinase domain; an α-helix

Full CDK9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDK9 p.Arg225Cys Pathogenic/Likely pathogenic ★★ same type
CDK9 c.175-7C>T Benign ★★ same type
CDK9 p.Ala173= Benign/Likely benign ★★ same type
CDK9 p.Ile292= Likely benign ★★ same type
CDK9 p.Ala288Thr Uncertain significance ★ ⚠ same type
CDK9 p.Ala36Gly Uncertain significance ★ ⚠ same type
CDK9 p.Arg273Trp Uncertain significance ★ ⚠ same type
CDK9 p.Arg303Gly 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/cdk9-p-val129met (accessed [today's date]).

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