Is TH p.Ala70= (c.210T>C) pathogenic?

TH p.Ala70= (c.210T>C) is classified Benign in TH (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-03). Common (popmax 12.7%, afr) — too common for a highly-penetrant pathogenic allele; Associated with TH-deficient dopa-responsive dystonia.

What condition is associated with TH p.Ala70= (c.210T>C)?

TH p.Ala70= (c.210T>C) is associated with TH-deficient dopa-responsive dystonia (ClinVar).

How is Autosomal recessive dopa-responsive dystonia inherited?

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

TH p.Ala70=

Q: How common is TH p.Ala70= (c.210T>C) in the general population?

TH p.Ala70= (c.210T>C) is common (popmax 12.7%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.210T>C · rs7950050 · VCV263253

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 12.7%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

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 -7	GERP -1.4
Overall
CADD	0.606	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 12.7% African / African-American · 9,559/75,038 alleles

Filtering AF 12.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 12.4%

Overall 0.723% 11,664/1,612,568 alleles · common exomes 6,145/1,460,282 · genomes 5,519/152,286 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	12.7%	8
Middle Eastern	1.66%	60
Admixed American	1.09%	92
Remaining individualsnot grpmax-eligible	1.08%	93
European (non-Finnish)	0.053%	1,888
South Asian	0.0505%	1,979
Ashkenazi Jewishnot grpmax-eligible	0.0169%	5,919
East Asian	0.00223%	44,852

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: TH
Protein: p.Ala70=
Coding: c.210T>C
MANE Select: NM_000360
dbSNP: rs7950050
Type: single nucleotide variant
Location: chr11:2169752 (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 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
TH c.90+13G>A 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-ala70 (accessed [today's date]).

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