G728S

AlphaMissense: likely benign (0.18)Uncertain significanceLumenal · predictedσ-1 candidate

Glycine → Serine at position 728 · C-terminal ER-lumenal (calcium binding, calmodulin, chaperone) · WFS1 (Wolframin)

Interactive 3D Structure

Interactive structure

rotate · zoom · variant + 5 Å neighbors

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Computational Predictions

AlphaMissense

0.178

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 conditionsInborn genetic diseases; Wolfram syndrome 1

Population frequency (gnomAD v4)Ultra-rare · AF 0.0019%

cDNA changec.2182G>A

ClinVar accessionVCV000130750

Last evaluated2025/04/14 00:00

Observed at very low frequency in gnomAD.

Full Variant Card

G728S — WFS1 Molecular Atlas Card

Variant type: Missense Substitution: Glycine (G) → Serine (S) at position 728 Domain context: C-terminal ER-lumenal (calcium binding, calmodulin, chaperone)

AlphaMissense

Pathogenicity score: 0.178
Class: likely benign

AlphaFold confidence

pLDDT at residue 728: 86.0

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: Inborn genetic diseases; Wolfram syndrome 1
cDNA change: c.2182G>A
ClinVar accession: VCV000130750
Last evaluated: 2025/04/14 00:00
Submissions: 1

Card generated by wolfram-atlas-batch (missense AlphaMissense mint) on 2026-06-08T02:27:33.730556Z. AlphaMissense (Cheng et al. 2023) · AlphaFold model v6 · UniProt O76024.

Therapeutic Strategy Handoff · prediction

Feed this card to Wolfram Intelligence

Download the G728S 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 G728S PDF card ↓Strategies are AI-generated predictions, not validated therapeutics.