Is CUL9 p.Asp945Val (c.2834A>T) pathogenic?

CUL9 p.Asp945Val (c.2834A>T) is classified Uncertain significance in CUL9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-07). AlphaMissense: likely benign (0.1377); Ultra-rare (popmax 0.0495%, mid).

How common is CUL9 p.Asp945Val (c.2834A>T) in the general population?

CUL9 p.Asp945Val (c.2834A>T) is ultra-rare (popmax 0.0495%, mid) (gnomAD).

What do computational predictors say about CUL9 p.Asp945Val (c.2834A>T)?

AlphaMissense predicts likely benign (score 0.1377) — an in-silico prediction, not a clinical call.

CUL9 p.Asp945Val

c.2834A>T · VCV4236152

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1377 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1377	likely benign
REVEL	0.136	moderately benign-leaning
SaProt	LLR -6.18	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.35 · evaluated, not missing
Pangolin	Δ0.29	loss · gain 0.00 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 3.2	GERP 1.6, phastCons 0.99
Regional constraint	o/e 0.80	unconstrained · MANE · 36 kb · p 3.2e-27 · regional, not allelic
Overall
CADD	20.2	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 0.0495% Middle Eastern · 3/6,062 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0129%

Overall 0.00242% 39/1,614,120 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0495%	2,021
South Asian	0.0231%	4,337
Admixed American	0.005%	20,003
Remaining individualsnot grpmax-eligible	0.0048%	20,837
Finnishnot grpmax-eligible	0.00469%	21,342
European (non-Finnish)	0.000508%	196,669

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.Asp945Val
Coding: c.2834A>T
MANE Select: NM_015089
Type: single nucleotide variant
Location: chr6:43198639 (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

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-asp945val (accessed [today's date]).

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