Is DRD2 p.Arg360His (c.1079G>A) pathogenic?

DRD2 p.Arg360His (c.1079G>A) is classified Conflicting classifications of pathogenicity in DRD2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-10-24). AlphaMissense: likely benign (0.2107); Ultra-rare (popmax 0.0514%, nfe); Associated with dystonic disorder.

What condition is associated with DRD2 p.Arg360His (c.1079G>A)?

DRD2 p.Arg360His (c.1079G>A) is associated with dystonic disorder (ClinVar).

How common is DRD2 p.Arg360His (c.1079G>A) in the general population?

DRD2 p.Arg360His (c.1079G>A) is ultra-rare (popmax 0.0514%, nfe) (gnomAD).

What do computational predictors say about DRD2 p.Arg360His (c.1079G>A)?

AlphaMissense predicts likely benign (score 0.2107) — an in-silico prediction, not a clinical call.

DRD2 p.Arg360His

c.1079G>A · rs138873192 · VCV1428794

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2107 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0514%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

dystonic disorder

Computational evidence

Protein change
AlphaMissense	0.2107	likely benign
REVEL	0.249	benign-leaning
SaProt	LLR -7.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	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 0.0514% European (non-Finnish) · 607/1,180,040 alleles

Filtering AF 0.048% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0466%

Overall 0.039% 630/1,614,020 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0514%	1,944
Middle Eastern	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.016%	6,249
Finnishnot grpmax-eligible	0.0125%	8,002
Admixed American	0.00333%	30,001
African / African-American	0.00267%	37,451

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.Arg360His
Coding: c.1079G>A
MANE Select: NM_000795
dbSNP: rs138873192
Type: single nucleotide variant
Location: chr11:113412615 (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.Arg360Cys Uncertain significance ★ ⚠ 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-arg360his (accessed [today's date]).

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