Sugi Variant
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TH/p.Ala474fs

TH p.Ala474fs

c.1420del · rs2495782383 · VCV2584914

Likely pathogenic Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Not reported
no gnomAD frequency available for this variant
Conditions
1
TH-deficient dopa-responsive dystonia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequenceframeshiftpredicted loss-of-function
NMDescapespremature termination codon in the last exon (13 of 13) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI—not assessed · substitutions only
Constraint at this position
ConservationphyloP 5.9GERP 1.2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene
TH
Protein
p.Ala474fs
Coding
c.1420del
MANE Select
NM_000360
dbSNP
rs2495782383
Type
Deletion
Location
chr11:2164307 (GRCh38)
Gene constraint
LOEUF 1.27 · pLI <0.01 (gnomAD)
Structure
AlphaFold pLDDT 81.75 · 7 PDB
Residue 474
an α-helix
Full TH gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

TH-deficient dopa-responsive dystonia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal recessive dopa-responsive dystonia (Orphanet):

Inheritance
Autosomal recessive
Onset
Infancy, Neonatal

Similar variants

  • TH p.Ala474= Conflicting classifications of pathogenicity ★ same residue
  • TH p.Gln346fs Pathogenic/Likely pathogenic ★★ same condition
  • TH p.Glu375fs Pathogenic/Likely pathogenic ★★ same condition
  • TH p.His335fs Likely pathogenic ★★ same condition
  • TH p.Ser195fs Pathogenic/Likely pathogenic ★★ same condition
  • TH p.Ser404fs Pathogenic/Likely pathogenic ★★ same condition
  • TH p.Thr238fs Pathogenic/Likely pathogenic ★★ same condition
  • TH p.Val18fs Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/th-p-ala474fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown