Is CUL9 p.Val1926= (c.5778C>T) pathogenic?

CUL9 p.Val1926= (c.5778C>T) is classified Benign in CUL9 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-17). Low-frequency (popmax 2.98%, nfe); Associated with CUL9-related disorder.

What condition is associated with CUL9 p.Val1926= (c.5778C>T)?

CUL9 p.Val1926= (c.5778C>T) is associated with CUL9-related disorder (ClinVar).

How common is CUL9 p.Val1926= (c.5778C>T) in the general population?

CUL9 p.Val1926= (c.5778C>T) is low-frequency (popmax 2.98%, nfe) (gnomAD).

CUL9 p.Val1926=

c.5778C>T · rs76552409 · VCV3060432

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 2.98%, nfe)

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 -1.8	GERP -1.4
Overall
CADD	8.364	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.98% European (non-Finnish) · 35,195/1,180,008 alleles

Filtering AF 2.96% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.95%

Overall 2.51% 40,444/1,614,188 alleles · low-frequency

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	11.1%	9
Finnishnot grpmax-eligible	3.77%	27
European (non-Finnish)grpmax	2.98%	34
Remaining individualsnot grpmax-eligible	2.11%	47
Ashkenazi Jewishnot grpmax-eligible	0.773%	129
Admixed American	0.685%	146
South Asian	0.473%	211
African / African-American	0.441%	227
Middle Eastern	0.132%	758
East Asian	0.00668%	14,960

Amish 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.Val1926=
Coding: c.5778C>T
MANE Select: NM_015089
dbSNP: rs76552409
Type: single nucleotide variant
Location: chr6:43215168 (GRCh38)
Gene constraint: LOEUF 0.334 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.64 · 4 PDB
Residue 1926: an α-helix

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-val1926 (accessed [today's date]).

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