Is TH p.Pro32= (c.96G>C) pathogenic?

TH p.Pro32= (c.96G>C) is classified Likely benign in TH (ClinVar, Single submitter, 1 submitter; last evaluated 2020-06-02). Absent from gnomAD v4.1; Associated with TH-deficient dopa-responsive dystonia.

What condition is associated with TH p.Pro32= (c.96G>C)?

TH p.Pro32= (c.96G>C) is associated with TH-deficient dopa-responsive dystonia (ClinVar).

How common is TH p.Pro32= (c.96G>C) in the general population?

TH p.Pro32= (c.96G>C) is absent from gnomAD v4.1 (gnomAD).

How is Autosomal recessive dopa-responsive dystonia inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

TH p.Pro32=

c.96G>C · rs202167640 · VCV1139556

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

TH-deficient dopa-responsive dystonia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.20	acceptor gain · deltas
Pangolin	Δ0.23	gain · loss 0.11 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -20	GERP -1.4
Overall
CADD	0.31	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.Pro32=
Coding: c.96G>C
MANE Select: NM_000360
dbSNP: rs202167640
Type: single nucleotide variant
Location: chr11:2169866 (GRCh38)
Gene constraint: LOEUF 1.27 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.75 · 7 PDB

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.Pro32Leu Uncertain significance ★ ⚠ 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-pro32 (accessed [today's date]).

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