Is DRD2 p.Leu141= (c.423G>A) pathogenic?

DRD2 p.Leu141= (c.423G>A) is classified Benign/Likely benign in DRD2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-28). Low-frequency (popmax 3.84%, nfe); Associated with dystonic disorder.

What condition is associated with DRD2 p.Leu141= (c.423G>A)?

DRD2 p.Leu141= (c.423G>A) is associated with dystonic disorder (ClinVar).

How common is DRD2 p.Leu141= (c.423G>A) in the general population?

DRD2 p.Leu141= (c.423G>A) is low-frequency (popmax 3.84%, nfe) (gnomAD).

DRD2 p.Leu141=

c.423G>A · rs1800499 · VCV238185

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.84%, nfe)

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 0.31	GERP -4.1, phastCons 0.98
Overall
CADD	8.069	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.84% European (non-Finnish) · 45,344/1,179,978 alleles

Filtering AF 3.81% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.8%

Overall 3.42% 55,154/1,614,058 alleles · low-frequency

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	5.15%	19
European (non-Finnish)grpmax	3.84%	26
Remaining individualsnot grpmax-eligible	3.4%	29
South Asian	3.26%	31
Middle Eastern	3.1%	32
Finnishnot grpmax-eligible	2.53%	40
Admixed American	1.51%	66
African / African-American	0.622%	161
Amishnot grpmax-eligible	0.11%	912
East Asian	0.00668%	14,959

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.Leu141=
Coding: c.423G>A
MANE Select: NM_000795
dbSNP: rs1800499
Type: single nucleotide variant
Location: chr11:113416972 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.49 · 11 PDB
Residue 141: a disulfide bond; 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.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-leu141 (accessed [today's date]).

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