Is CUL9 p.Pro2324= (c.6972C>G) pathogenic?

CUL9 p.Pro2324= (c.6972C>G) is classified Benign in CUL9 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-13). Low-frequency (popmax 1.08%, sas); Associated with CUL9-related disorder.

What condition is associated with CUL9 p.Pro2324= (c.6972C>G)?

CUL9 p.Pro2324= (c.6972C>G) is associated with CUL9-related disorder (ClinVar).

How common is CUL9 p.Pro2324= (c.6972C>G) in the general population?

CUL9 p.Pro2324= (c.6972C>G) is low-frequency (popmax 1.08%, sas) (gnomAD).

CUL9 p.Pro2324=

c.6972C>G · rs573445870 · VCV3041405

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.08%, sas)

Conditions

CUL9-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 -2.7	GERP -2.9
Overall
CADD	2.679	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.08% South Asian · 981/91,086 alleles

Filtering AF 1.02% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.999%

Overall 0.0637% 1,028/1,613,640 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.08%	93
Remaining individualsnot grpmax-eligible	0.0592%	1,689
Middle Eastern	0.033%	3,031
East Asian	0.00446%	22,445
African / African-American	0.00266%	37,527
Admixed American	0.00167%	60,020
European (non-Finnish)	0.000254%	393,337

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: CUL9
Protein: p.Pro2324=
Coding: c.6972C>G
MANE Select: NM_015089
dbSNP: rs573445870
Type: single nucleotide variant
Location: chr6:43222581 (GRCh38)
Gene constraint: LOEUF 0.334 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.64 · 4 PDB

Full CUL9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CUL9-related disorder

Similar variants

CUL9 p.Cys2171Trp Uncertain significance ★ ⚠ same condition
CUL9 p.Thr2301Ile Uncertain significance ★ ⚠ same condition
CUL9 p.Ala2306Val Uncertain significance ⚠ same condition
CUL9 p.Arg102= Uncertain significance same condition
CUL9 c.2389-7C>A Likely benign same condition
CUL9 c.3051-8C>T Benign same condition
CUL9 c.3384+9C>T Likely benign same condition
CUL9 c.5023-7C>T 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/cul9-p-pro2324 (accessed [today's date]).

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