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F783=

SynonymousSilentLikely benignLumenal · predicted
Synonymous variant · codon at position 783 · C-terminal ER-lumenal (calcium binding, calmodulin, chaperone) · WFS1 (Wolframin)

Silent — Silent — no amino-acid change

Interactive 3D Structure

Interactive structure
rotate · zoom · variant + 5 Å neighbors
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AlphaFold wild-type wolframin · the variant site near residue 783 (C-terminal ER-lumenal (calcium binding, calmodulin, chaperone)) is highlighted.

Variant Assessment

Variant type
Synonymous
Schema
Silent
Silent — no amino-acid change
Domain
C-terminal ER-lumenal (calcium binding, calmodulin, chaperone)
Status
—

Therapeutic Implication · Silent

No amino-acid change (F783 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

ClinVar classificationLikely benign
Review statuscriteria provided, multiple submitters, no conflicts
Associated conditionsCataract 41; Wolfram-like syndrome; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus
Population frequency (gnomAD v4)Ultra-rare · AF 0.0012%
cDNA changec.2349C>T
Protein consequenceF783=
ClinVar variantNM_006005.3(WFS1):c.2349C>T (p.Phe783=)
ClinVar accessionVCV001589906
Last evaluated2022/10/24 00:00

Observed at very low frequency in gnomAD.

Classified for2★ documented assertion

ClinVar classifies this variant as Likely benign for Cataract 41 (autosomal dominant, OMIM 116400); Wolfram-like syndrome (autosomal dominant, OMIM 614296); Wolfram syndrome (classic) (autosomal recessive, OMIM 222300); Nonsyndromic hearing loss (DFNA6/14/38) (autosomal dominant, OMIM 600965); WFS1-related diabetes (autosomal dominant). These are two clinically distinct disease families: classic Wolfram syndrome requires two affected copies, while the dominant WFS1-related disorders do not. One label covers both, and it does not tell you which applies to a given person.

  • Cataract 41autosomal dominant · OMIM 116400submitted as: Cataract 41
  • Wolfram-like syndromeautosomal dominant · OMIM 614296submitted as: Wolfram-like syndrome
  • Wolfram syndrome (classic)autosomal recessive · OMIM 222300submitted as: Wolfram syndrome 1
  • Nonsyndromic hearing loss (DFNA6/14/38)autosomal dominant · OMIM 600965submitted as: Autosomal dominant nonsyndromic hearing loss 6
  • WFS1-related diabetesautosomal dominantsubmitted as: Type 2 diabetes mellitus
  • 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.

Population frequency
Global (all ancestries)
AF 0.0012% · 17 / 1,460,604 alleles
Homozygotes
0
Highest-frequency population
European (non-Finnish) · AF 0.0014%

Highest in European (non-Finnish): AF 0.0014% (16 of 1,111,954 alleles), in line with the global figure.

No homozygotes reported in gnomAD v4. For a recessive allele this is expected and is not, on its own, evidence either way.

Ancestry groupAllele freq.AC / ANHom.Carrier est.
Finnish · under-sampled0.0019%1 / 52,2280—
European (non-Finnish)0.0014%16 / 1,111,9540~1 in 34750

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.

Therapeutic Strategy Handoff · prediction

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Full Variant Card

F783= — WFS1 Molecular Atlas Card

Variant type: Synonymous (silent) Codon: position 783 (Phenylalanine, F) — 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 (F783 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

Likely benign — for Cataract 41 (autosomal dominant, OMIM 116400); Wolfram-like syndrome (autosomal dominant, OMIM 614296); Wolfram syndrome (classic) (autosomal recessive, OMIM 222300); Nonsyndromic hearing loss (DFNA6/14/38) (autosomal dominant, OMIM 600965); WFS1-related diabetes (autosomal dominant)

ClinVar classifies this variant as Likely benign for Cataract 41 (autosomal dominant, OMIM 116400); Wolfram-like syndrome (autosomal dominant, OMIM 614296); Wolfram syndrome (classic) (autosomal recessive, OMIM 222300); Nonsyndromic hearing loss (DFNA6/14/38) (autosomal dominant, OMIM 600965); WFS1-related diabetes (autosomal dominant). These are two clinically distinct disease families: classic Wolfram syndrome requires two affected copies, while the dominant WFS1-related disorders do not. One label covers both, and it does not tell you which applies to a given person.

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: Likely benign
  • Review status: criteria provided, multiple submitters, no conflicts
  • Associated conditions: Cataract 41; Wolfram-like syndrome; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus
  • cDNA change: c.2349C>T
  • ClinVar accession: VCV001589906
  • Last evaluated: 2022/10/24 00:00
  • Submissions: 1

Card generated by wolfram-atlas-batch (synonymous pipeline) on 2026-06-08T02:56:13.054889Z. WFS1: UniProt O76024, AlphaFold v6. Synonymous variants carry no protein-structural effect.