G789S

Category 5 — IDR ExclusionConflictingLumenal · predictedσ-1 candidateEditorial

Glycine → Serine at position 789 · C-terminal lumenal domain (653-869) · WFS1 (Wolframin)

Gly→Ser p789 IDR AM=0.07 ddg=-0.11 pLDDT=43. ClinVar Conflicting evidence. Atlas mechanism: see structural analysis.

Interactive 3D Structure

Wild-type reference

Wild-type G789 — hydrogen bond to A787

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DynaMut2 mutant · G789S

Mutant S789 — hydrogen bond to A787 lost (2 contacts lost)

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Bond changes · DynaMut2 interaction analysis

2 lost0 gained3 preserved

Interaction type	Wild-type partner	Mutant partner	Status
Hydrogen bond	A787	—	Lost
Hydrogen bond	R791	R791	Preserved
Polar contact	A787	A787	Preserved
Polar contact	R791	R791	Preserved
Van der Waals	R791	—	Lost

Lost / gained / preserved interatomic contacts at the variant residue, from the DynaMut2 (Arpeggio) interaction analysis of the wild-type and energy-minimized mutant structures.

Computational Predictions

DynaMut2 ΔΔG

-0.11kcal/mol

Destabilising — mild

AlphaMissense

0.069

LBen

AlphaFold pLDDT

model confidence

Schema

Cat 5

Category 5 — IDR Exclusion

Clinical Evidence

ClinVar classificationConflicting classifications of pathogenicity

Review statuscriteria provided, conflicting classifications

Associated conditions(no specific conditions catalogued)

InheritanceConflicting ClinVar classifications.

Population frequency (gnomAD v4)Ultra-rare · AF 0.0033%

cDNA changec.2365G>A

ClinVar accessionVCV001419650

Last evaluated2025/08/30 00:00

Observed at very low frequency in gnomAD.

Structural Context

Position analysis: SER790 (2.5 Å — partner of S790W/L), ASP788 (2.5 Å), ALA787 (4.5 Å — A787T). pLDDT 43 IDR boundary. Position 789 adjacent to multi-substitution 790. The Atlas's neighbor extraction surfaces this variant's contacts and connects them to the broader multi-variant target landscape.

Amino-acid chemistry

glycine flexibility lost

Position in the protein

C-terminal lumenal IDR

Druggability Assessment

Cat 5 IDR — see structural prose. AlphaMissense below threshold (AM under-call class) but mechanism is structurally identified. Therapeutic strategy: site-directed at contacts identified above, or wet-lab validation if pLDDT borderline/below 50.

Why this matters

IDR boundary near S790 cluster.

Therapeutic Strategy Handoff · prediction

Feed this card to Wolfram Intelligence

Download the G789S PDF below and upload it to Wolfram Intelligence to generate therapeutic-strategy proposals — guanidinium mimetics, sigma-1 agonist docking, NAC thiol-capping. NAC is already on the bench-testing list.

Download G789S PDF card ↓Strategies are AI-generated predictions, not validated therapeutics.

UniProt Domain Annotation

Chain1–890 · Wolframin

Topological domain653–869 · Lumenal