K811=
SynonymousSilentBenignLumenal · predictedSilent — Silent — no amino-acid change
Interactive 3D Structure
AlphaFold wild-type wolframin · the variant site near residue 811 (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); WFS1-related diabetes (autosomal dominant); Hearing loss, inheritance unstated (inheritance not specified); 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
- WFS1-related diabetesautosomal dominantsubmitted as: Diabetes mellitus
- Hearing loss, inheritance unstatedinheritance not specifiedsubmitted as: Sensorineural hearing loss disorder
- 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 95.47% (42782 of 44,810 alleles), in line with the global figure.
298167 homozygotes reported in gnomAD v4 (20460 East Asian; 15411 Admixed American; 6730 Ashkenazi Jewish; 18510 South Asian; 12109 Remaining individuals; 1100 Middle Eastern; 204125 European (non-Finnish); 10083 Finnish; 9569 African / African American; 70 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 | 95.47% | 42,782 / 44,810 | 20460 | ~1 in 1 |
| Admixed American | 71.32% | 42,730 / 59,916 | 15411 | ~1 in 1 |
| Ashkenazi Jewish | 67.48% | 19,898 / 29,486 | 6730 | ~1 in 1 |
| South Asian | 63.42% | 57,637 / 90,880 | 18510 | ~1 in 1 |
| Remaining individuals | 62.16% | 38,747 / 62,338 | 12109 | ~1 in 1 |
| Middle Eastern | 59.19% | 3,581 / 6,050 | 1100 | ~1 in 1 |
| European (non-Finnish) | 58.89% | 693,420 / 1,177,502 | 204125 | ~1 in 1 |
| Finnish | 56.69% | 35,232 / 62,146 | 10083 | ~1 in 1 |
| African / African American | 50.25% | 37,650 / 74,932 | 9569 | ~1 in 1 |
| Amish | 39.07% | 354 / 906 | 70 | ~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
K811= — WFS1 Molecular Atlas Card
Variant type: Synonymous (silent) Codon: position 811 (Lysine, K) — 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 (K811 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); WFS1-related diabetes (autosomal dominant); Hearing loss, inheritance unstated (inheritance not specified); 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); WFS1-related diabetes (autosomal dominant); Hearing loss, inheritance unstated (inheritance not specified); 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; Diabetes mellitus; Sensorineural hearing loss disorder; Autosomal dominant nonsyndromic hearing loss 6
- cDNA change: c.2433G>A
- ClinVar accession: VCV000045455
- Last evaluated: 2026/02/04 00:00
- Submissions: 1
Card generated by wolfram-atlas-batch (synonymous pipeline) on 2026-06-08T02:56:27.720308Z.
WFS1: UniProt O76024, AlphaFold v6. Synonymous variants carry no protein-structural effect.