Is CDK9 p.Pro321= (c.963C>T) pathogenic?

CDK9 p.Pro321= (c.963C>T) is classified Likely benign in CDK9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-27). Ultra-rare (popmax 0.0329%, mid).

How common is CDK9 p.Pro321= (c.963C>T) in the general population?

CDK9 p.Pro321= (c.963C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

CDK9 p.Pro321=

c.963C>T · VCV4904603

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

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 0.15	GERP -3.2, phastCons 0.94
Overall
CADD	5.907	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.00297% 48/1,613,936 alleles · ultra-rare exomes 45/1,461,746 · genomes 3/152,190 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
Remaining individualsnot grpmax-eligible	0.016%	6,249
East Asian	0.00445%	22,448
European (non-Finnish)	0.00288%	34,707

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.Pro321=
Coding: c.963C>T
MANE Select: NM_001261
Type: single nucleotide variant
Location: chr9:127789387 (GRCh38)
Gene constraint: LOEUF 1.139 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 28 PDB

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

Similar variants

CDK9 p.Pro321Ser Uncertain significance ★ ⚠ same residue
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

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-pro321 (accessed [today's date]).

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