Is CUL9 p.Ala2145= (c.6435G>A) pathogenic?

CUL9 p.Ala2145= (c.6435G>A) is classified Benign in CUL9 (ClinVar, Single submitter, 2 submitters; last evaluated 2018-01-31). Rare (popmax 0.433%, nfe).

How common is CUL9 p.Ala2145= (c.6435G>A) in the general population?

CUL9 p.Ala2145= (c.6435G>A) is rare (popmax 0.433%, nfe) (gnomAD).

CUL9 p.Ala2145=

c.6435G>A · rs143347950 · VCV782249

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.433%, nfe)

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 -0.74	GERP -3.2, phastCons 0.003
Overall
CADD	7.207	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.433% European (non-Finnish) · 5,112/1,179,882 alleles

Filtering AF 0.423% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.419%

Overall 0.401% 6,473/1,612,618 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.26%	79
European (non-Finnish)grpmax	0.433%	231
Remaining individualsnot grpmax-eligible	0.367%	273
Admixed American	0.23%	435
Middle Eastern	0.206%	485
South Asian	0.147%	679
African / African-American	0.064%	1,563
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,792
East Asian	0.00223%	44,878

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala2145=
Coding: c.6435G>A
MANE Select: NM_015089
dbSNP: rs143347950
Type: single nucleotide variant
Location: chr6:43220758 (GRCh38)
Gene constraint: LOEUF 0.334 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.64 · 4 PDB
Residue 2145: the 'triad supradomain' region

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

Similar variants

CUL9 p.Ala2145Val Uncertain significance ★ ⚠ same residue
CUL9 p.Glu617Lys Likely benign ★★ ⚠ same type
CUL9 c.1987+2T>C Uncertain significance ★ same type
CUL9 p.Ala1004Val Uncertain significance ★ ⚠ same type
CUL9 p.Ala1093Pro Uncertain significance ★ ⚠ same type
CUL9 p.Ala1112Thr Uncertain significance ★ ⚠ same type
CUL9 p.Ala111Thr Uncertain significance ★ ⚠ same type
CUL9 p.Ala121Glu 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/cul9-p-ala2145 (accessed [today's date]).

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