S790L

Category 5 — IDR ExclusionConflictingLumenal · predictedσ-1 candidateEditorial

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

Ser→Leu p790 lumenal AM=0.09 ddg=-0.6 pLDDT=42. ClinVar Conflicting evidence. Atlas mechanism: see structural analysis.

Interactive 3D Structure

Wild-type reference

Wild-type S790 — hydrogen bond to D788

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DynaMut2 mutant · S790L

Mutant L790 — 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

-0.60kcal/mol

Destabilising — mild

AlphaMissense

0.095

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)Low frequency · AF 0.011%

cDNA changec.2369C>T

ClinVar accessionVCV000229641

Last evaluated2025/11/26 00:00

Observed in the general population.

Structural Context

Position analysis: GLY789 (2.4 Å), ARG791 (2.4 Å), ASP788 (3.9 Å). pLDDT 42 deep IDR. Same position as S790W. DynaMut2 untrustworthy. The Atlas's neighbor extraction surfaces this variant's contacts and connects them to the broader multi-variant target landscape.

Amino-acid chemistry

polar→hydrophobic

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

Same position as S790W — deep IDR.

Therapeutic Strategy Handoff · prediction

Feed this card to Wolfram Intelligence

Download the S790L 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 S790L PDF card ↓Strategies are AI-generated predictions, not validated therapeutics.

UniProt Domain Annotation

Chain1–890 · Wolframin

Topological domain653–869 · Lumenal