Is DRD2 p.Arg360Cys (c.1078C>T) pathogenic?

DRD2 p.Arg360Cys (c.1078C>T) is classified Uncertain significance in DRD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-16). AlphaMissense: ambiguous (0.3924); Very rare (popmax 0.00167%, amr); Associated with dystonic disorder.

What condition is associated with DRD2 p.Arg360Cys (c.1078C>T)?

DRD2 p.Arg360Cys (c.1078C>T) is associated with dystonic disorder (ClinVar).

How common is DRD2 p.Arg360Cys (c.1078C>T) in the general population?

DRD2 p.Arg360Cys (c.1078C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DRD2 p.Arg360Cys (c.1078C>T)?

AlphaMissense predicts ambiguous (score 0.3924) — an in-silico prediction, not a clinical call.

DRD2 p.Arg360Cys

c.1078C>T · VCV3715527

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3924 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

dystonic disorder

Computational evidence

Protein change
AlphaMissense	0.3924	ambiguous
REVEL	0.352	indeterminate
SaProt	LLR -10.75	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.49	unconstrained · MANE · 1,939 bp · p 3.2e-09 · regional, not allelic
Overall
CADD	33.0	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 0.00167% Admixed American · 1/59,990 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.00105% 17/1,614,014 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
Remaining individualsnot grpmax-eligible	0.0032%	31,243
Admixed Americangrpmax	0.00167%	59,990
African / African-American	0.00133%	74,910
European (non-Finnish)	0.00102%	98,337

Ashkenazi Jewish 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: DRD2
Protein: p.Arg360Cys
Coding: c.1078C>T
MANE Select: NM_000795
Type: single nucleotide variant
Location: chr11:113412616 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.49 · 11 PDB
Residue 360: the 'interaction with ppp1r9b' region

Full DRD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

dystonic disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DRD2 p.Arg360His Conflicting classifications of pathogenicity ★ ⚠ same residue
DRD2 p.Arg274Gln Uncertain significance ★★ ⚠ same condition
DRD2 p.Gln366Lys Uncertain significance ★★ ⚠ same condition
DRD2 p.Glu99Lys Uncertain significance ★★ ⚠ same condition
DRD2 p.Gly261Arg Uncertain significance ★★ ⚠ same condition
DRD2 p.His316Pro Uncertain significance ★★ ⚠ same condition
DRD2 p.Ile431Thr Uncertain significance ★★ ⚠ same condition
DRD2 p.Pro300His Uncertain significance ★★ ⚠ 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/drd2-p-arg360cys (accessed [today's date]).

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