Is DRD2 p.Gln366Lys (c.1096C>A) pathogenic?

DRD2 p.Gln366Lys (c.1096C>A) is classified Uncertain significance in DRD2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-29). AlphaMissense: likely benign (0.2651); Ultra-rare (popmax 0.0133%, amr); Associated with dystonic disorder.

What condition is associated with DRD2 p.Gln366Lys (c.1096C>A)?

DRD2 p.Gln366Lys (c.1096C>A) is associated with dystonic disorder (ClinVar).

How common is DRD2 p.Gln366Lys (c.1096C>A) in the general population?

DRD2 p.Gln366Lys (c.1096C>A) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

What do computational predictors say about DRD2 p.Gln366Lys (c.1096C>A)?

AlphaMissense predicts likely benign (score 0.2651) — an in-silico prediction, not a clinical call.

DRD2 p.Gln366Lys

c.1096C>A · rs779477138 · VCV654937

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2651 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

dystonic disorder

Computational evidence

Protein change
AlphaMissense	0.2651	likely benign
REVEL	0.357	indeterminate
SaProt	LLR -5.87	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.49	unconstrained · MANE · 1,939 bp · p 3.2e-09 · regional, not allelic
Overall
CADD	23.3	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 0.0133% Admixed American · 8/60,008 alleles

Filtering AF 0.00661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00482%

Overall 0.000743% 12/1,614,030 alleles · ultra-rare exomes 7/1,461,876 · genomes 5/152,154 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0133%	7,501
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)	0.000254%	393,345

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.Gln366Lys
Coding: c.1096C>A
MANE Select: NM_000795
dbSNP: rs779477138
Type: single nucleotide variant
Location: chr11:113412598 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.49 · 11 PDB
Residue 366: the 'interaction with ppp1r9b' region; an α-helix

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.Arg274Gln 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
DRD2 c.285+7G>A 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-gln366lys (accessed [today's date]).

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