Is CUL4B p.Pro78Ala (c.232C>G) pathogenic?

CUL4B p.Pro78Ala (c.232C>G) is classified Uncertain significance in CUL4B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-05-24). AlphaMissense: likely benign (0.057); Absent from gnomAD v4.1; Associated with CUL4B-related disorder.

What condition is associated with CUL4B p.Pro78Ala (c.232C>G)?

CUL4B p.Pro78Ala (c.232C>G) is associated with CUL4B-related disorder (ClinVar).

How common is CUL4B p.Pro78Ala (c.232C>G) in the general population?

CUL4B p.Pro78Ala (c.232C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CUL4B p.Pro78Ala (c.232C>G)?

AlphaMissense predicts likely benign (score 0.057) — an in-silico prediction, not a clinical call.

CUL4B p.Pro78Ala

c.232C>G · VCV3345182

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.057 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CUL4B-related disorder

Computational evidence

Protein change
AlphaMissense	0.057	likely benign
REVEL	0.139	moderately benign-leaning
SaProt	LLR -5.44	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 1.7, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 495 bp · p 0.069 · regional, not allelic
Overall
CADD	21.0	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P96A vs ClinVar P78A) — verify the residue.

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: CUL4B
Protein: p.Pro78Ala
Coding: c.232C>G
MANE Select: NM_001079872
Type: single nucleotide variant
Location: chrX:120560407 (GRCh38)
Structure: AlphaFold pLDDT 80.02 · 5 PDB
Residue 96 UniProt numbering: the 'disordered' region

Full CUL4B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CUL4B-related disorder

Similar variants

CUL4B c.1852+1G>T Pathogenic ★ same condition
CUL4B c.2267-2A>G Likely pathogenic ★ same condition
CUL4B p.Ile318Ser Uncertain significance ★ ⚠ same condition
CUL4B p.Ser456Phe Uncertain significance ★ ⚠ same condition
CUL4B p.Glu221Asp Uncertain significance ⚠ same condition
CUL4B p.Lys782Arg Uncertain significance ⚠ same condition
CUL4B p.Pro681Leu Uncertain significance ⚠ same condition
CUL4B p.Thr67Ile Uncertain significance ⚠ 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/cul4b-p-pro78ala (accessed [today's date]).

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