Is CUL9 p.Arg1102Gln (c.3305G>A) pathogenic?

CUL9 p.Arg1102Gln (c.3305G>A) is classified Uncertain significance in CUL9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely benign (0.0886); Rare (popmax 0.109%, sas).

How common is CUL9 p.Arg1102Gln (c.3305G>A) in the general population?

CUL9 p.Arg1102Gln (c.3305G>A) is rare (popmax 0.109%, sas) (gnomAD).

What do computational predictors say about CUL9 p.Arg1102Gln (c.3305G>A)?

AlphaMissense predicts likely benign (score 0.0886) — an in-silico prediction, not a clinical call.

CUL9 p.Arg1102Gln

c.3305G>A · rs375384551 · VCV2515405

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0886 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.109%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0886	likely benign
REVEL	0.318	indeterminate
SaProt	LLR -6.47	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 0.66, phastCons 0.66
Regional constraint	o/e 0.80	unconstrained · MANE · 36 kb · p 3.2e-27 · regional, not allelic
Overall
CADD	21.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.109% South Asian · 99/91,080 alleles

Filtering AF 0.0913% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0849%

Overall 0.00812% 131/1,614,162 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.109%	920
East Asian	0.0134%	7,481
Admixed American	0.005%	20,006
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
African / African-American	0.00267%	37,519
European (non-Finnish)	0.00169%	59,001

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.Arg1102Gln
Coding: c.3305G>A
MANE Select: NM_015089
dbSNP: rs375384551
Type: single nucleotide variant
Location: chr6:43200077 (GRCh38)
Gene constraint: LOEUF 0.334 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.64 · 4 PDB
Residue 1102: an α-helix

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

Similar variants

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
CUL9 p.Ala131Val 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-arg1102gln (accessed [today's date]).

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