S855P

Category 5 — IDR ExclusionConflictingLumenal · predictedσ-1 candidateEditorial

Serine → Proline at position 855 · C-terminal lumenal domain (653-869) · WFS1 (Wolframin)

Ser→Pro p855 lumenal AM=0.09 ddg=-0.08 pLDDT=45. ClinVar Conflicting evidence. Atlas mechanism: see structural analysis.

Interactive 3D Structure

Wild-type reference

Wild-type S855 — hydrogen bond to T857

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DynaMut2 mutant · S855P

Mutant P855 — polar contact contact to T857 lost

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Bond changes · DynaMut2 interaction analysis

0 lost2 gained2 preserved

Interaction type	Wild-type partner	Mutant partner	Status
Hydrogen bond	—	Q853	Gained
Hydrogen bond	T857	T857	Preserved
Polar contact	—	Q853	Gained
Polar contact	T857	T857	Preserved

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

-0.08kcal/mol

Destabilising — mild

AlphaMissense

0.091

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)Absent from gnomAD v4

cDNA changec.2563_2565delinsCCG

ClinVar accessionVCV000591341

Last evaluated2020/07/18 00:00

Not observed in ~730k individuals — consistent with a rare allele (ACMG PM2_supporting).

Structural Context

Position analysis: LEU854 (2.5 Å), PRO856 (2.5 Å — adjacent existing P! Pro-Pro motif!), THR857 (4.1 Å). Pro-Pro motif created at 855-856. pLDDT 45 IDR boundary. The Atlas's neighbor extraction surfaces this variant's contacts.

Amino-acid chemistry

proline introduction

Position in the protein

C-terminal lumenal domain

Druggability Assessment

Cat 5 IDR boundary — see structural prose. AlphaMissense below threshold (AM under-call class) but mechanism is structurally clear from neighbor analysis. Therapeutic strategy: site-directed at the contacts identified above.

Why this matters

Pro-Pro motif at IDR boundary.

Therapeutic Strategy Handoff · prediction

Feed this card to Wolfram Intelligence

Download the S855P 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 S855P PDF card ↓Strategies are AI-generated predictions, not validated therapeutics.

UniProt Domain Annotation

Chain1–890 · Wolframin

Topological domain653–869 · Lumenal