S544=
SynonymousSilentLikely benignTransmembrane · predictedSilent — Silent — no amino-acid change
Interactive 3D Structure
AlphaFold wild-type wolframin · the variant site near residue 544 (Transmembrane helix 8) is highlighted.
Variant Assessment
Therapeutic Implication · Silent
Clinical Evidence
Observed in the general population.
ClinVar classifies this variant as Benign/Likely benign 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.
Highest in Middle Eastern: AF 0.049% (3 of 6,062 alleles), in line with the global figure.
1 homozygote reported in gnomAD v4 (1 Remaining individuals). 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. |
|---|---|---|---|---|
| Middle Eastern | 0.049% | 3 / 6,062 | 0 | ~1 in 1010 |
| European (non-Finnish) | 0.034% | 401 / 1,180,040 | 0 | ~1 in 1470 |
| Remaining individuals | 0.027% | 17 / 62,498 | 1 | ~1 in 1840 |
| East Asian | 0.027% | 12 / 44,882 | 0 | ~1 in 1870 |
| South Asian | 0.016% | 15 / 91,090 | 0 | ~1 in 3040 |
| Admixed American | 0.013% | 8 / 60,034 | 0 | ~1 in 3750 |
| African / African American | 0.011% | 8 / 75,068 | 0 | ~1 in 4690 |
| Finnish | 0.0048% | 3 / 62,236 | 0 | ~1 in 10370 |
| Ashkenazi Jewish · under-sampled | 0.0034% | 1 / 29,608 | 0 | — |
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.
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Full Variant Card
S544= — WFS1 Molecular Atlas Card
Variant type: Synonymous (silent) Codon: position 544 (Serine, S) — amino acid unchanged Domain context: Transmembrane helix 8
Schema category: Silent — Silent — no amino-acid change
No amino-acid change (S544 is unchanged): the codon is altered but the protein sequence is identical to wild-type. No structural, stability or AlphaMissense effect applies. Synonymous variants are typically benign unless they affect splicing or regulatory elements; this one is not adjacent to an exon boundary.
Clinical evidence
Inheritance and scope
Benign/Likely benign — for Wolfram syndrome (classic) (autosomal recessive, OMIM 222300)
ClinVar classifies this variant as Benign/Likely benign 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: Benign/Likely benign
- Review status: criteria provided, multiple submitters, no conflicts
- Associated conditions: Wolfram syndrome 1
- cDNA change: c.1632C>T
- ClinVar accession: VCV000178593
- Last evaluated: 2026/01/23 00:00
- Submissions: 1
Card generated by wolfram-atlas-batch (synonymous pipeline) on 2026-06-08T02:54:24.477236Z.
WFS1: UniProt O76024, AlphaFold v6. Synonymous variants carry no protein-structural effect.