Is CUL9 p.Asp2211= (c.6633C>T) pathogenic?

CUL9 p.Asp2211= (c.6633C>T) is classified Benign in CUL9 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-04). Common (popmax 46.8%, afr) — too common for a highly-penetrant pathogenic allele; Associated with CUL9-related disorder.

What condition is associated with CUL9 p.Asp2211= (c.6633C>T)?

CUL9 p.Asp2211= (c.6633C>T) is associated with CUL9-related disorder (ClinVar).

CUL9 p.Asp2211=

Q: How common is CUL9 p.Asp2211= (c.6633C>T) in the general population?

CUL9 p.Asp2211= (c.6633C>T) is common (popmax 46.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.6633C>T · rs6917902 · VCV3060566

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 46.8%, afr) — too common for a highly-penetrant pathogenic allele

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 -9.6	GERP -3.5
Overall
CADD	0.059	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 46.8% African / African-American · 35,011/74,822 alleles

Filtering AF 46.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 46.2%

Overall 16.8% 271,386/1,610,922 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	46.8%	2
Amishnot grpmax-eligible	26.3%	4
Remaining individualsnot grpmax-eligible	16.6%	6
European (non-Finnish)	16.3%	6
Admixed American	15.7%	6
Middle Eastern	13.1%	8
Ashkenazi Jewishnot grpmax-eligible	12.6%	8
South Asian	12.3%	8
Finnishnot grpmax-eligible	11.4%	9
East Asian	1.91%	52

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.Asp2211=
Coding: c.6633C>T
MANE Select: NM_015089
dbSNP: rs6917902
Type: single nucleotide variant
Location: chr6:43221202 (GRCh38)
Gene constraint: LOEUF 0.334 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.64 · 4 PDB
Residue 2211: the 'triad supradomain' region

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-asp2211 (accessed [today's date]).

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