Is CDK9 p.Ala288Thr (c.862G>A) pathogenic?

CDK9 p.Ala288Thr (c.862G>A) is classified Uncertain significance in CDK9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-17). AlphaMissense: likely pathogenic (0.9311); Ultra-rare (popmax 0.0646%, eas); Associated with CDK9-related disorder.

What condition is associated with CDK9 p.Ala288Thr (c.862G>A)?

CDK9 p.Ala288Thr (c.862G>A) is associated with CDK9-related disorder (ClinVar).

How common is CDK9 p.Ala288Thr (c.862G>A) in the general population?

CDK9 p.Ala288Thr (c.862G>A) is ultra-rare (popmax 0.0646%, eas) (gnomAD).

What do computational predictors say about CDK9 p.Ala288Thr (c.862G>A)?

AlphaMissense predicts likely pathogenic (score 0.9311) — an in-silico prediction, not a clinical call.

CDK9 p.Ala288Thr

c.862G>A · VCV4855432

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9311 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0646%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CDK9-related disorder

Computational evidence

Protein change
AlphaMissense	0.9311	likely pathogenic
REVEL	0.715	pathogenic-leaning
SaProt	LLR -11.59	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	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	27.6	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

Grpmax group 0.0646% East Asian · 29/44,892 alleles

Filtering AF 0.0461% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0399%

Overall 0.00229% 37/1,613,812 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0646%	1,548
South Asian	0.0011%	91,084
European (non-Finnish)	0.000593%	168,576

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: CDK9
Protein: p.Ala288Thr
Coding: c.862G>A
MANE Select: NM_001261
Type: single nucleotide variant
Location: chr9:127789286 (GRCh38)
Gene constraint: LOEUF 1.139 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 28 PDB
Residue 288: the protein kinase domain; an α-helix

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

Disease context

CDK9-related disorder

Similar variants

CDK9 p.Leu118Ser Uncertain significance ⚠ same condition
CDK9 p.Met219Thr Uncertain significance ⚠ same condition
CDK9 c.175-3C>T Likely benign same condition
CDK9 c.433-6C>T Benign same condition
CDK9 p.Ala361= Likely benign same condition
CDK9 p.Cys106= Likely benign same condition
CDK9 p.Glu203Ter Likely benign same condition
CDK9 p.Thr354= Likely benign 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/cdk9-p-ala288thr (accessed [today's date]).

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