Is CDK9 p.Thr362Ala (c.1084A>G) pathogenic?

CDK9 p.Thr362Ala (c.1084A>G) is classified Uncertain significance in CDK9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: likely benign (0.0514); Ultra-rare (popmax 0.0533%, amr).

How common is CDK9 p.Thr362Ala (c.1084A>G) in the general population?

CDK9 p.Thr362Ala (c.1084A>G) is ultra-rare (popmax 0.0533%, amr) (gnomAD).

What do computational predictors say about CDK9 p.Thr362Ala (c.1084A>G)?

AlphaMissense predicts likely benign (score 0.0514) — an in-silico prediction, not a clinical call.

CDK9 p.Thr362Ala

c.1084A>G · VCV3999702

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0514 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0533%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0514	likely benign
REVEL	0.189	benign-leaning
SaProt	LLR -6.26	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	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	16.76	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 0.0533% Admixed American · 32/60,006 alleles

Filtering AF 0.0387% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0339%

Overall 0.00198% 32/1,613,990 alleles · ultra-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: CDK9
Protein: p.Thr362Ala
Coding: c.1084A>G
MANE Select: NM_001261
Type: single nucleotide variant
Location: chr9:127789508 (GRCh38)
Gene constraint: LOEUF 1.139 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 28 PDB
Residue 362: a modified residue (phosphothreonine; by cdk9); the 'disordered' region

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-thr362ala (accessed [today's date]).

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