Is CUL9 p.Ala683= (c.2049G>A) pathogenic?

CUL9 p.Ala683= (c.2049G>A) is classified Benign in CUL9 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-21). Low-frequency (popmax 1.63%, afr); Associated with CUL9-related disorder.

What condition is associated with CUL9 p.Ala683= (c.2049G>A)?

CUL9 p.Ala683= (c.2049G>A) is associated with CUL9-related disorder (ClinVar).

How common is CUL9 p.Ala683= (c.2049G>A) in the general population?

CUL9 p.Ala683= (c.2049G>A) is low-frequency (popmax 1.63%, afr) (gnomAD).

CUL9 p.Ala683=

c.2049G>A · rs142912012 · VCV3038922

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.63%, afr)

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 -8.1	GERP -3.3
Overall
CADD	0.629	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.63% African / African-American · 1,225/75,034 alleles

Filtering AF 1.56% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.53%

Overall 0.0893% 1,442/1,614,150 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.63%	61
Middle Eastern	0.264%	379
Remaining individualsnot grpmax-eligible	0.134%	744
Admixed American	0.11%	909
South Asian	0.0296%	3,373
East Asian	0.00668%	14,964
European (non-Finnish)	0.00178%	56,192

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.Ala683=
Coding: c.2049G>A
MANE Select: NM_015089
dbSNP: rs142912012
Type: single nucleotide variant
Location: chr6:43188584 (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.Ala683Thr Uncertain significance ★ ⚠ same residue
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

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-ala683 (accessed [today's date]).

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