R285H

AlphaMissense: likely benign (0.07)Likely benignCytoplasmic · predicted

Arginine → Histidine at position 285 · N-terminal cytoplasmic (intrinsically disordered) · WFS1 (Wolframin)

Interactive 3D Structure

Interactive structure

rotate · zoom · variant + 5 Å neighbors

Fullscreen ↗

Computational Predictions

AlphaMissense

0.067

likely benign

AlphaFold pLDDT

model confidence

DynaMut2 ΔΔG

pending

not yet computed

ClinVar

Likely benign

Benign/Likely benign

AlphaMissense + AlphaFold card. This variant is mapped from AlphaMissense pathogenicity and AlphaFold confidence. The DynaMut2 ΔΔG stability prediction and the wild-type/mutant structural comparison (dual-pane + bond network) are computed per-variant and backfill here — they require a DynaMut2 submission, unlike the precomputed AlphaMissense score.

Clinical Evidence

ClinVar classificationBenign/Likely benign

Review statuscriteria provided, multiple submitters, no conflicts

Associated conditionsWolfram syndrome 1; Wolfram-like syndrome; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Cataract 41; WFS1-Related Spectrum Disorders

Population frequency (gnomAD v4)Low frequency · AF 0.040%

cDNA changec.854G>A

ClinVar accessionVCV000178587

Last evaluated2026/01/19 00:00

Observed in the general population.

Full Variant Card

R285H — WFS1 Molecular Atlas Card

Variant type: Missense Substitution: Arginine (R) → Histidine (H) at position 285 Domain context: N-terminal cytoplasmic (intrinsically disordered)

AlphaMissense

Pathogenicity score: 0.0674
Class: likely benign

AlphaFold confidence

pLDDT at residue 285: 54.34

DynaMut2 ΔΔG: not yet computed for this variant — AlphaMissense + AlphaFold confidence shown above. Stability ΔΔG and the wild-type/mutant structural comparison backfill behind this note.

Clinical evidence

Classification: Benign/Likely benign
Review status: criteria provided, multiple submitters, no conflicts
Associated conditions: Wolfram syndrome 1; Wolfram-like syndrome; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Cataract 41; WFS1-Related Spectrum Disorders
cDNA change: c.854G>A
ClinVar accession: VCV000178587
Last evaluated: 2026/01/19 00:00
Submissions: 1

Card generated by wolfram-atlas-batch (missense AlphaMissense mint) on 2026-06-08T02:27:33.433655Z. AlphaMissense (Cheng et al. 2023) · AlphaFold model v6 · UniProt O76024.

Therapeutic Strategy Handoff · prediction

Feed this card to Wolfram Intelligence

Download the R285H 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 R285H PDF card ↓Strategies are AI-generated predictions, not validated therapeutics.