Is DRD2 p.Arg274Gln (c.821G>A) pathogenic?

DRD2 p.Arg274Gln (c.821G>A) is classified Uncertain significance in DRD2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-18). AlphaMissense: likely benign (0.0723); Ultra-rare (popmax 0.029%, eas); Associated with dystonic disorder.

What condition is associated with DRD2 p.Arg274Gln (c.821G>A)?

DRD2 p.Arg274Gln (c.821G>A) is associated with dystonic disorder (ClinVar).

How common is DRD2 p.Arg274Gln (c.821G>A) in the general population?

DRD2 p.Arg274Gln (c.821G>A) is ultra-rare (popmax 0.029%, eas) (gnomAD).

What do computational predictors say about DRD2 p.Arg274Gln (c.821G>A)?

AlphaMissense predicts likely benign (score 0.0723) — an in-silico prediction, not a clinical call.

DRD2 p.Arg274Gln

c.821G>A · rs200184730 · VCV1046844

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0723 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.029%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

dystonic disorder

Computational evidence

Protein change
AlphaMissense	0.0723	likely benign
REVEL	0.085	moderately benign-leaning
SaProt	LLR -6.55	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 2,833 bp · p 0.35 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.029% East Asian · 13/44,852 alleles

Filtering AF 0.0171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00236% 38/1,611,122 alleles · ultra-rare exomes 35/1,459,022 · genomes 3/152,100 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.029%	3,450
Finnishnot grpmax-eligible	0.00791%	12,646
African / African-American	0.00534%	18,713
Remaining individualsnot grpmax-eligible	0.00321%	31,145
European (non-Finnish)	0.0011%	90,752
South Asian	0.0011%	90,958

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.Arg274Gln
Coding: c.821G>A
MANE Select: NM_000795
dbSNP: rs200184730
Type: single nucleotide variant
Location: chr11:113412873 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.49 · 11 PDB
Residue 274: 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.Arg274Trp Uncertain significance ★ ⚠ same residue
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
DRD2 c.1139-653A>C Benign ★★ 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-arg274gln (accessed [today's date]).

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