Is CDK9 p.Thr354= (c.1062C>T) pathogenic?

CDK9 p.Thr354= (c.1062C>T) is classified Likely benign in CDK9 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-11-27). Ultra-rare (popmax 0.0493%, mid); Associated with CDK9-related disorder.

What condition is associated with CDK9 p.Thr354= (c.1062C>T)?

CDK9 p.Thr354= (c.1062C>T) is associated with CDK9-related disorder (ClinVar).

How common is CDK9 p.Thr354= (c.1062C>T) in the general population?

CDK9 p.Thr354= (c.1062C>T) is ultra-rare (popmax 0.0493%, mid) (gnomAD).

CDK9 p.Thr354=

c.1062C>T · rs770616688 · VCV3054575

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, mid)

Conditions

CDK9-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.59	GERP 0.52, phastCons 1
Overall
CADD	10.06	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0493% Middle Eastern · 3/6,084 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00715%

Overall 0.000867% 14/1,614,008 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0493%	2,028
African / African-American	0.004%	24,973
European (non-Finnish)	0.000678%	147,505

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.Thr354=
Coding: c.1062C>T
MANE Select: NM_001261
dbSNP: rs770616688
Type: single nucleotide variant
Location: chr9:127789486 (GRCh38)
Gene constraint: LOEUF 1.139 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 28 PDB
Residue 354: a modified residue (phosphothreonine; by cdk9); the 'disordered' region

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

Disease context

CDK9-related disorder

Similar variants

CDK9 p.Ala288Thr Uncertain significance ★ ⚠ same condition
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

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-thr354 (accessed [today's date]).

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