Is CUL9 p.Leu1848= (c.5544G>A) pathogenic?

CUL9 p.Leu1848= (c.5544G>A) is classified Likely benign in CUL9 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-06). Very rare (popmax 0.00212%, nfe); Associated with CUL9-related disorder.

What condition is associated with CUL9 p.Leu1848= (c.5544G>A)?

CUL9 p.Leu1848= (c.5544G>A) is associated with CUL9-related disorder (ClinVar).

How common is CUL9 p.Leu1848= (c.5544G>A) in the general population?

CUL9 p.Leu1848= (c.5544G>A) is very rare (popmax 0.00212%, nfe) (gnomAD).

CUL9 p.Leu1848=

c.5544G>A · rs766066895 · VCV3039774

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00212%, nfe)

Conditions

CUL9-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.29 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.51	GERP 0.67, phastCons 0.22
Overall
CADD	11.58	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00212% European (non-Finnish) · 25/1,180,056 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00167% 27/1,613,992 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00212%	47,202
African / African-American	0.00133%	74,922
South Asian	0.0011%	91,078

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.Leu1848=
Coding: c.5544G>A
MANE Select: NM_015089
dbSNP: rs766066895
Type: single nucleotide variant
Location: chr6:43213768 (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-leu1848 (accessed [today's date]).

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