Is DRD1 p.Thr37Met (c.110C>T) pathogenic?

DRD1 p.Thr37Met (c.110C>T) is classified Conflicting classifications of pathogenicity in DRD1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-04-09). AlphaMissense: likely pathogenic (0.8196); Very rare (popmax 0.000339%, nfe); Associated with parkinsonism-dystonia, infantile.

What condition is associated with DRD1 p.Thr37Met (c.110C>T)?

DRD1 p.Thr37Met (c.110C>T) is associated with parkinsonism-dystonia, infantile (ClinVar).

How common is DRD1 p.Thr37Met (c.110C>T) in the general population?

DRD1 p.Thr37Met (c.110C>T) is very rare (popmax 0.000339%, nfe) (gnomAD).

How is Infantile dystonia-parkinsonism inherited?

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

What do computational predictors say about DRD1 p.Thr37Met (c.110C>T)?

AlphaMissense predicts likely pathogenic (score 0.8196) — an in-silico prediction, not a clinical call.

DRD1 p.Thr37Met

c.110C>T · VCV4072307

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8196 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

parkinsonism-dystonia, infantile

Computational evidence

Protein change
AlphaMissense	0.8196	likely pathogenic
REVEL	0.62	indeterminate
SaProt	LLR -12.67	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 578 bp · p 2e-14 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,180,044 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,613,984 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00156%	64,010
European (non-Finnish)grpmax	0.000339%	295,011

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DRD1
Protein: p.Thr37Met
Coding: c.110C>T
MANE Select: NM_000794
Type: single nucleotide variant
Location: chr5:175442990 (GRCh38)
Gene constraint: LOEUF 0.252 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.23 · 34 PDB
Residue 37: a UniProt-annotated variant site (in); an α-helix

Full DRD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

parkinsonism-dystonia, infantile — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Infantile dystonia-parkinsonism (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

DRD1 c.-48G>A Likely benign ★★ same type
DRD1 p.Ala147Thr Uncertain significance ★ ⚠ same type
DRD1 p.Ala166Thr Uncertain significance ★ ⚠ same type
DRD1 p.Ala410Ser Uncertain significance ★ ⚠ same type
DRD1 p.Ala67Ser Uncertain significance ★ ⚠ same type
DRD1 p.Arg52Pro Uncertain significance ★ ⚠ same type
DRD1 p.Asn185Lys Uncertain significance ★ ⚠ same type
DRD1 p.Cys253Ser Uncertain significance ★ ⚠ same type

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/drd1-p-thr37met (accessed [today's date]).

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