T117M
AlphaMissense: likely benign (0.08)Likely benignCytoplasmic · 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
Observed in the general population.
ClinVar classifies this variant as Benign/Likely benign for WFS1-related diabetes (autosomal dominant). These are dominant WFS1-related disorders and are clinically distinct from classic recessive Wolfram syndrome. This classification is not a statement about Wolfram syndrome severity.
- WFS1-related diabetesautosomal dominantsubmitted as: Diabetes mellitus; Monogenic diabetes
- 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.
Highest in African / African American: AF 0.865% (649 of 74,994 alleles), 17.2x the global figure. The global AF describes the general population, not the at-risk group.
6 homozygotes reported in gnomAD v4 (6 African / African American). gnomAD excludes individuals with severe pediatric disease, so homozygotes in this dataset argue against a fully penetrant severe recessive phenotype and belong in the clinical picture. This is interpretive signal, not a classification.
| Ancestry group | Allele freq. | AC / AN | Hom. | Carrier est. |
|---|---|---|---|---|
| African / African American | 0.865% | 649 / 74,994 | 6 | ~1 in 58 |
| Remaining individuals | 0.058% | 36 / 62,300 | 0 | ~1 in 870 |
| Admixed American | 0.049% | 29 / 59,326 | 0 | ~1 in 1020 |
| Middle Eastern | 0.033% | 2 / 6,056 | 0 | ~1 in 1510 |
| South Asian | 0.015% | 13 / 89,458 | 0 | ~1 in 3440 |
| European (non-Finnish) | 0.0070% | 82 / 1,177,658 | 0 | ~1 in 7180 |
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
T117M — WFS1 Molecular Atlas Card
Variant type: Missense Substitution: Threonine (T) → Methionine (M) at position 117 Domain context: N-terminal cytoplasmic (intrinsically disordered)
AlphaMissense
- Pathogenicity score: 0.0836
- Class: likely benign
AlphaFold confidence
- pLDDT at residue 117: 78.25
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
Benign/Likely benign — for WFS1-related diabetes (autosomal dominant)
ClinVar classifies this variant as Benign/Likely benign for WFS1-related diabetes (autosomal dominant). These are dominant WFS1-related disorders and are clinically distinct from classic recessive Wolfram syndrome. This classification is not a statement about Wolfram syndrome severity.
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: Benign/Likely benign
- Review status: criteria provided, multiple submitters, no conflicts
- Associated conditions: Diabetes mellitus; Monogenic diabetes
- cDNA change: c.350C>T
- ClinVar accession: VCV000045457
- Last evaluated: 2026/01/25 00:00
- Submissions: 1
Card generated by wolfram-atlas-batch (missense AlphaMissense mint) on 2026-06-08T02:27:33.362168Z.
AlphaMissense (Cheng et al. 2023) · AlphaFold model v6 · UniProt O76024.
Feed this card to Wolfram Intelligence
Download the T117M 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.