S790W

Category 5 — IDR ExclusionConflictingLumenal · predictedσ-1 candidateEditorial

Serine → Tryptophan at position 790 · C-terminal lumenal domain (653-869) · WFS1 (Wolframin)

Serine → Tryptophan at position 790. ClinVar Conflicting including Wolfram. AlphaMissense 0.15 (below threshold) — AM under-call. DynaMut2 ΔΔG -0.81. pLDDT 42 — Category 5 IDR!

Interactive 3D Structure

Wild-type reference

Wild-type S790 — hydrogen bond to D788

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DynaMut2 mutant · S790W

Mutant W790 — energy-minimized; 1 new contact formed

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Bond changes · DynaMut2 interaction analysis

0 lost1 gained4 preserved

Interaction type	Wild-type partner	Mutant partner	Status
Hydrogen bond	D788	D788	Preserved
Hydrogen bond	S792	S792	Preserved
Polar contact	D788	D788	Preserved
Polar contact	S792	S792	Preserved
Van der Waals	—	S792	Gained

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

-0.81kcal/mol

Destabilising — mild

AlphaMissense

0.145

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 conditionsWolfram syndrome 1

InheritanceWolfram syndrome 1.

Population frequency (gnomAD v4)Ultra-rare · AF 0.0047%

cDNA changec.2369C>G

ClinVar accessionVCV000166608

Last evaluated2025/10/01 00:00

Observed at very low frequency in gnomAD.

Structural Context

Position 790 at pLDDT 42 — DEEP IDR. Sparse neighbors (GLY789, ARG791, ASP788). DynaMut2 untrustworthy.

S790W introduces massive aromatic volume into a disordered region. AM 0.15 under-call. Wolfram documented.

Amino-acid chemistry

Serine (S) → Tryptophan (W) — small polar hydroxyl replaced by bulky aromatic indole. Massive volume increase.

Position in the protein

C-terminal lumenal domain · position 790 (pLDDT 42 — deep IDR).

Druggability Assessment

Category 5 — IDR Exclusion. pLDDT 42 deep IDR. AlphaMissense 0.15 below threshold. DynaMut2 prediction not trustworthy.

The Atlas routes Category 5 variants to wet-lab characterization.

Why this matters

S790W is deep-IDR — Atlas flags for wet-lab work.

Therapeutic Strategy Handoff · prediction

Feed this card to Wolfram Intelligence

Download the S790W 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 S790W PDF card ↓Strategies are AI-generated predictions, not validated therapeutics.

UniProt Domain Annotation

Chain1–890 · Wolframin

Topological domain653–869 · Lumenal