F884Y
AlphaMissense: likely benign (0.11)Uncertain significanceTransmembrane · predictedInteractive 3D Structure
Computational Predictions
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
Not observed in ~730k individuals — consistent with a rare allele (ACMG PM2_supporting).
ClinVar classifies this variant as Uncertain significance for Wolfram syndrome (classic) (autosomal recessive, OMIM 222300). Classic Wolfram syndrome is recessive: a single copy does not produce it, and this classification says nothing about a carrier's own risk.
- Wolfram syndrome (classic)autosomal recessive · OMIM 222300submitted as: Wolfram syndrome 1
- Phenotype scope is interpretation of submitted records. The computed values on this card (AlphaMissense, DynaMut2 ΔΔG, pLDDT) are measurements of the model, not of a patient.
- Presentation cannot be generalised from neighbouring variants: one nucleotide over can present very differently. Structural similarity supports a mechanistic hypothesis, never a phenotype claim.
Review status: 2★ multiple submitters, no conflicts. ClinVar "conditions" is the union of all submissions; 0–1★ entries are submitted conditions, not documented phenotypes.
No population breakdown — the variant is absent from gnomAD v4, so no ancestry group has an observed frequency.
No homozygotes — the variant is absent from gnomAD v4 altogether.
Source: gnomAD r4, retrieved 2026-08-21. Values are allele frequencies. The carrier estimate is derived from the allele frequency (Hardy-Weinberg, ~2·AF) and is an approximation, not a published figure — where a published carrier frequency exists it outranks this column and is cited on the card.
Full Variant Card
F884Y — WFS1 Molecular Atlas Card
Variant type: Missense Substitution: Phenylalanine (F) → Tyrosine (Y) at position 884 Domain context: C-terminal ER-lumenal (calcium binding, calmodulin, chaperone)
AlphaMissense
- Pathogenicity score: 0.1064
- Class: likely benign
AlphaFold confidence
- pLDDT at residue 884: 75.56
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
Inheritance and scope
Uncertain significance — for Wolfram syndrome (classic) (autosomal recessive, OMIM 222300)
ClinVar classifies this variant as Uncertain significance for Wolfram syndrome (classic) (autosomal recessive, OMIM 222300). Classic Wolfram syndrome is recessive: a single copy does not produce it, and this classification says nothing about a carrier's own risk.
Phenotype scope is interpretation of submitted records. The computed values on this card (AlphaMissense, DynaMut2 ΔΔG, pLDDT) are measurements of the model, not of a patient. Presentation cannot be generalised from neighbouring variants: one nucleotide over can present very differently. Structural similarity supports a mechanistic hypothesis, never a phenotype claim.
- Classification: Uncertain significance
- Review status: criteria provided, multiple submitters, no conflicts
- Associated conditions: Wolfram syndrome 1
- cDNA change: c.2651T>A
- ClinVar accession: VCV000215404
- Last evaluated: 2025/07/21 00:00
- Submissions: 1
Card generated by wolfram-atlas-batch (missense AlphaMissense mint) on 2026-06-08T02:27:33.842882Z.
AlphaMissense (Cheng et al. 2023) · AlphaFold model v6 · UniProt O76024.
Feed this card to Wolfram Intelligence
Download the F884Y 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.