Is TH p.Asp467= (c.1401C>T) pathogenic?

TH p.Asp467= (c.1401C>T) is classified Benign/Likely benign in TH (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). Common (popmax 7.88%, afr) — too common for a highly-penetrant pathogenic allele; Associated with TH-deficient dopa-responsive dystonia.

What condition is associated with TH p.Asp467= (c.1401C>T)?

TH p.Asp467= (c.1401C>T) 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.Asp467=

Q: How common is TH p.Asp467= (c.1401C>T) in the general population?

TH p.Asp467= (c.1401C>T) is common (popmax 7.88%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1401C>T · rs3842724 · VCV304066

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 7.88%, 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 -4.2	GERP -3.4
Overall
CADD	0.432	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.88% African / African-American · 5,667/71,928 alleles

Filtering AF 7.71% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.64%

Overall 0.497% 7,663/1,540,704 alleles · common exomes 3,982/1,388,376 · genomes 3,681/152,328 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.88%	13
Middle Eastern	1.01%	99
Admixed American	0.92%	109
Remaining individualsnot grpmax-eligible	0.686%	146
Ashkenazi Jewishnot grpmax-eligible	0.344%	291
European (non-Finnish)	0.0829%	1,206
South Asian	0.0268%	3,732

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.Asp467=
Coding: c.1401C>T
MANE Select: NM_000360
dbSNP: rs3842724
Type: single nucleotide variant
Location: chr11:2164326 (GRCh38)
Gene constraint: LOEUF 1.27 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.75 · 7 PDB
Residue 467: a UniProt-annotated variant site (in arsegs; loss of over 80% of tyrosine 3-monooxygenase activity)

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.Asp467Gly Pathogenic/Likely pathogenic ★★ ⚠ same residue
TH p.Asp467Tyr Likely pathogenic ★ ⚠ same residue
TH p.Asp467Glu 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

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-asp467 (accessed [today's date]).

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