TH p.Ser19=
c.57T>C · rs2495842706 · VCV2179529
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
TH-deficient dopa-responsive dystonia
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -10 | GERP -1.8 |
| Overall | ||
| CADD | 0.219 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- TH
- Protein
- p.Ser19=
- Coding
- c.57T>C
- MANE Select
- NM_000360
- dbSNP
- rs2495842706
- Type
- single nucleotide variant
- Location
- chr11:2171730 (GRCh38)
- Gene constraint
- LOEUF 1.27 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.75 · 7 PDB
- Residue 19
- a UniProt-annotated variant site (found in a patient with arsegs; uncertain significance); a modified residue (phosphoserine; by camk2)
Disease context
TH-deficient dopa-responsive dystonia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Autosomal recessive dopa-responsive dystonia (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Infancy, Neonatal
Similar variants
- TH p.Ser19Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
- TH c.1200+2T>C Likely pathogenic ★★ same condition
- TH c.1334+1G>A Likely pathogenic ★★ same condition
- TH c.312+1G>A Likely pathogenic ★★ same condition
- TH c.488-1G>A Pathogenic ★★ same condition
- TH c.644+1G>A Likely pathogenic ★★ same condition
- TH c.695+1G>C Likely pathogenic ★★ same condition
- TH c.90+10C>T 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-ser19 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown