Is CUL9 p.Ala533Pro (c.1597G>C) pathogenic?

CUL9 p.Ala533Pro (c.1597G>C) is classified Uncertain significance in CUL9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-07). AlphaMissense: likely benign (0.1145); Absent from gnomAD v4.1.

How common is CUL9 p.Ala533Pro (c.1597G>C) in the general population?

CUL9 p.Ala533Pro (c.1597G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CUL9 p.Ala533Pro (c.1597G>C)?

AlphaMissense predicts likely benign (score 0.1145) — an in-silico prediction, not a clinical call.

CUL9 p.Ala533Pro

c.1597G>C · VCV4657699

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1145 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1145	likely benign
REVEL	0.306	indeterminate
SaProt	LLR -5.74	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 1.5	GERP -1.6, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 36 kb · p 3.2e-27 · regional, not allelic
Overall
CADD	13.65	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CUL9
Protein: p.Ala533Pro
Coding: c.1597G>C
MANE Select: NM_015089
Type: single nucleotide variant
Location: chr6:43187728 (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.Ala533Asp 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-ala533pro (accessed [today's date]).

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