Is DRD2 p.Leu284= (c.852C>T) pathogenic?

DRD2 p.Leu284= (c.852C>T) is classified Benign in DRD2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-12). Low-frequency (popmax 4.38%, afr); Associated with dystonic disorder.

What condition is associated with DRD2 p.Leu284= (c.852C>T)?

DRD2 p.Leu284= (c.852C>T) is associated with dystonic disorder (ClinVar).

How common is DRD2 p.Leu284= (c.852C>T) in the general population?

DRD2 p.Leu284= (c.852C>T) is low-frequency (popmax 4.38%, afr) (gnomAD).

DRD2 p.Leu284=

c.852C>T · rs4986921 · VCV695414

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.38%, afr)

Conditions

dystonic disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.97	GERP -4.1
Overall
CADD	3.48	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.38% African / African-American · 3,283/75,008 alleles

Filtering AF 4.25% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.2%

Overall 0.23% 3,708/1,613,034 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.38%	23
Admixed American	0.318%	314
Remaining individualsnot grpmax-eligible	0.303%	330
Middle Eastern	0.203%	493
South Asian	0.0143%	7,002
East Asian	0.00223%	44,850
European (non-Finnish)	0.0017%	58,994

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.Leu284=
Coding: c.852C>T
MANE Select: NM_000795
dbSNP: rs4986921
Type: single nucleotide variant
Location: chr11:113412842 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.49 · 11 PDB
Residue 284: the 'interaction with ppp1r9b' region; the 'disordered' 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.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
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-leu284 (accessed [today's date]).

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