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D788=

SynonymousSilentLikely benignLumenal · predicted
Synonymous variant · codon at position 788 · 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 788 (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 (D788 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 conditionsWolfram syndrome 1
Population frequency (gnomAD v4)Ultra-rare · AF 0.0070%
cDNA changec.2364C>T
Protein consequenceD788=
ClinVar variantNM_006005.3(WFS1):c.2364C>T (p.Asp788=)
ClinVar accessionVCV000259898
Last evaluated2026/01/04 00:00

Observed at very low frequency in gnomAD.

Classified for2★ documented assertion

ClinVar classifies this variant as 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.

Population frequency
Global (all ancestries)
AF 0.0070% · 113 / 1,612,834 alleles
Homozygotes
1
Highest-frequency population
African / African American · AF 0.067%

Highest in African / African American: AF 0.067% (50 of 75,068 alleles), 9.5x the global figure. The global AF describes the general population, not the at-risk group.

1 homozygote reported in gnomAD v4 (1 South Asian). 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 groupAllele freq.AC / ANHom.Carrier est.
African / African American0.067%50 / 75,0680~1 in 750
Admixed American0.047%28 / 60,0240~1 in 1070
Middle Eastern0.033%2 / 6,0620~1 in 1520
Remaining individuals0.011%7 / 62,4840~1 in 4460
South Asian0.0099%9 / 91,0881~1 in 5060
East Asian · under-sampled0.0022%1 / 44,8820—
Finnish · under-sampled0.0016%1 / 62,7300—
European (non-Finnish)0.0013%15 / 1,179,9880~1 in 39330

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

D788= — WFS1 Molecular Atlas Card

Variant type: Synonymous (silent) Codon: position 788 (Aspartic acid, D) — 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 (D788 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 Wolfram syndrome (classic) (autosomal recessive, OMIM 222300)

ClinVar classifies this variant as 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: Likely benign
  • Review status: criteria provided, multiple submitters, no conflicts
  • Associated conditions: Wolfram syndrome 1
  • cDNA change: c.2364C>T
  • ClinVar accession: VCV000259898
  • Last evaluated: 2026/01/04 00:00
  • Submissions: 1

Card generated by wolfram-atlas-batch (synonymous pipeline) on 2026-06-08T02:56:16.095926Z. WFS1: UniProt O76024, AlphaFold v6. Synonymous variants carry no protein-structural effect.