S855=
SynonymousSilentBenignLumenal · predictedSilent — Silent — no amino-acid change
Interactive 3D Structure
AlphaFold wild-type wolframin · the variant site near residue 855 (C-terminal ER-lumenal (calcium binding, calmodulin, chaperone)) is highlighted.
Variant Assessment
Therapeutic Implication · Silent
Clinical Evidence
Population frequency too high for a penetrant Wolfram allele — stand-alone benign evidence (ACMG BA1).
ClinVar classifies this variant as Benign for WFS1-related spectrum (unresolved mode) (dominant or recessive); Nonsyndromic hearing loss (DFNA6/14/38) (autosomal dominant, OMIM 600965). ClinVar records this under a WFS1-spectrum label that spans both disease families — recessive Wolfram syndrome (biallelic) and the dominant WFS1-related disorders. The label does not resolve which applies, and it is not a severity statement.
- WFS1-related spectrum (unresolved mode)dominant or recessivesubmitted as: WFS1-Related Spectrum Disorders
- Nonsyndromic hearing loss (DFNA6/14/38)autosomal dominant · OMIM 600965submitted as: Autosomal dominant nonsyndromic hearing loss 6
- 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 East Asian: AF 95.54% (42879 of 44,882 alleles), in line with the global figure.
397452 homozygotes reported in gnomAD v4 (20517 East Asian; 9205 Ashkenazi Jewish; 18182 Admixed American; 26782 South Asian; 21702 African / African American; 1775 Middle Eastern; 16232 Remaining individuals; 271400 European (non-Finnish); 11517 Finnish; 140 Amish). 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. |
|---|---|---|---|---|
| East Asian | 95.54% | 42,879 / 44,882 | 20517 | ~1 in 1 |
| Ashkenazi Jewish | 78.76% | 23,307 / 29,592 | 9205 | ~1 in 1 |
| Admixed American | 77.67% | 46,596 / 59,994 | 18182 | ~1 in 1 |
| South Asian | 76.47% | 69,644 / 91,068 | 26782 | ~1 in 1 |
| African / African American | 76.05% | 57,069 / 75,040 | 21702 | ~1 in 1 |
| Middle Eastern | 75.83% | 4,597 / 6,062 | 1775 | ~1 in 1 |
| Remaining individuals | 71.94% | 44,955 / 62,486 | 16232 | ~1 in 1 |
| European (non-Finnish) | 67.81% | 800,094 / 1,179,894 | 271400 | ~1 in 1 |
| Finnish | 60.34% | 37,887 / 62,786 | 11517 | ~1 in 1 |
| Amish | 56.83% | 516 / 908 | 140 | ~1 in 1 |
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
S855= — WFS1 Molecular Atlas Card
Variant type: Synonymous (silent) Codon: position 855 (Serine, S) — amino acid unchanged Domain context: C-terminal ER-lumenal (calcium binding, calmodulin, chaperone)
Schema category: Silent — Silent — no amino-acid change
No amino-acid change (S855 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 — for WFS1-related spectrum (unresolved mode) (dominant or recessive); Nonsyndromic hearing loss (DFNA6/14/38) (autosomal dominant, OMIM 600965)
ClinVar classifies this variant as Benign for WFS1-related spectrum (unresolved mode) (dominant or recessive); Nonsyndromic hearing loss (DFNA6/14/38) (autosomal dominant, OMIM 600965). ClinVar records this under a WFS1-spectrum label that spans both disease families — recessive Wolfram syndrome (biallelic) and the dominant WFS1-related disorders. The label does not resolve which applies, and it is not a severity statement.
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
- Review status: criteria provided, multiple submitters, no conflicts
- Associated conditions: WFS1-Related Spectrum Disorders; Autosomal dominant nonsyndromic hearing loss 6
- cDNA change: c.2565A>G
- ClinVar accession: VCV000045456
- Last evaluated: 2026/02/04 00:00
- Submissions: 1
Card generated by wolfram-atlas-batch (synonymous pipeline) on 2026-06-08T02:56:47.019706Z.
WFS1: UniProt O76024, AlphaFold v6. Synonymous variants carry no protein-structural effect.