A243T

AlphaMissense: likely benign (0.11)Uncertain significanceCytoplasmic · predicted

Alanine → Threonine at position 243 · N-terminal cytoplasmic (intrinsically disordered) · WFS1 (Wolframin)

Interactive 3D Structure

Interactive structure

rotate · zoom · variant + 5 Å neighbors

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Computational Predictions

AlphaMissense

0.109

likely benign

AlphaFold pLDDT

model confidence

DynaMut2 ΔΔG

pending

not yet computed

ClinVar

Uncertain significance

Uncertain significance/Uncertain risk allele

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 classificationUncertain significance/Uncertain risk allele

Review statuscriteria provided, multiple submitters, no conflicts

Associated conditionsCataract 41; Wolfram-like syndrome; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Inborn genetic diseases

Population frequency (gnomAD v4)Ultra-rare · AF 0.00087%

cDNA changec.727G>A

ClinVar accessionVCV000809616

Last evaluated2025/06/10 00:00

Observed at very low frequency in gnomAD.

Full Variant Card

A243T — WFS1 Molecular Atlas Card

Variant type: Missense Substitution: Alanine (A) → Threonine (T) at position 243 Domain context: N-terminal cytoplasmic (intrinsically disordered)

AlphaMissense

Pathogenicity score: 0.1094
Class: likely benign

AlphaFold confidence

pLDDT at residue 243: 86.19

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: Uncertain significance/Uncertain risk allele
Review status: criteria provided, multiple submitters, no conflicts
Associated conditions: Cataract 41; Wolfram-like syndrome; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Inborn genetic diseases
cDNA change: c.727G>A
ClinVar accession: VCV000809616
Last evaluated: 2025/06/10 00:00
Submissions: 1

Card generated by wolfram-atlas-batch (missense AlphaMissense mint) on 2026-06-08T02:27:33.417012Z. AlphaMissense (Cheng et al. 2023) · AlphaFold model v6 · UniProt O76024.

Therapeutic Strategy Handoff · prediction

Feed this card to Wolfram Intelligence

Download the A243T 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 A243T PDF card ↓Strategies are AI-generated predictions, not validated therapeutics.