A787T

Category 5 — IDR ExclusionConflictingLumenal · predictedσ-1 candidateEditorial

Alanine → Threonine at position 787 · C-terminal lumenal domain (653-869) · WFS1 (Wolframin)

Ala→Thr p787 lumenal AM=0.06 ddg=+0.05 pLDDT=45. ClinVar Conflicting evidence. Atlas mechanism: see structural analysis.

Interactive 3D Structure

Wild-type reference

Wild-type A787 — hydrogen bond to G789

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DynaMut2 mutant · A787T

Mutant T787 — hydrogen bond to G789 lost (3 contacts lost)

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Bond changes · DynaMut2 interaction analysis

3 lost0 gained0 preserved

Interaction type	Wild-type partner	Mutant partner	Status
Hydrogen bond	G789	—	Lost
Polar contact	S785	—	Lost
Polar contact	G789	—	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

0.05kcal/mol

Stabilising — mild

AlphaMissense

0.063

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 0.0079%

cDNA changec.2359G>A

ClinVar accessionVCV000444631

Last evaluated2026/01/09 00:00

Observed at very low frequency in gnomAD.

Structural Context

Position analysis: ASP788 (2.5 Å — partner of G789S!), GLY786 (2.6 Å), SER785 (4.4 Å). pLDDT 45 IDR boundary. Same region as S790L/W cluster. The Atlas's neighbor extraction surfaces this variant's contacts and connects them to the broader multi-variant target landscape.

Amino-acid chemistry

polarity introduced

Position in the protein

C-terminal lumenal IDR boundary

Druggability Assessment

Cat 5 IDR boundary — 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 A787T 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 A787T PDF card ↓Strategies are AI-generated predictions, not validated therapeutics.

UniProt Domain Annotation

Chain1–890 · Wolframin

Topological domain653–869 · Lumenal