Is DRD2 p.Asn176= (c.528C>T) pathogenic?

DRD2 p.Asn176= (c.528C>T) is classified Likely benign in DRD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-19). Very rare (popmax 0.00602%, nfe); Associated with dystonic disorder.

What condition is associated with DRD2 p.Asn176= (c.528C>T)?

DRD2 p.Asn176= (c.528C>T) is associated with dystonic disorder (ClinVar).

How common is DRD2 p.Asn176= (c.528C>T) in the general population?

DRD2 p.Asn176= (c.528C>T) is very rare (popmax 0.00602%, nfe) (gnomAD).

DRD2 p.Asn176=

c.528C>T · VCV3664881

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00602%, nfe)

Conditions

dystonic disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.87 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.1	GERP -0.84, phastCons 1
Overall
CADD	9.334	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00602% European (non-Finnish) · 71/1,179,896 alleles

Filtering AF 0.00486% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00447%

Overall 0.00533% 86/1,613,934 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00602%	16,618
South Asian	0.00549%	18,199
African / African-American	0.004%	25,024
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,596
Admixed American	0.00333%	30,003
Remaining individualsnot grpmax-eligible	0.0032%	31,249
East Asian	0.00223%	44,874
Finnishnot grpmax-eligible	0.00156%	64,026

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.Asn176=
Coding: c.528C>T
MANE Select: NM_000795
Type: single nucleotide variant
Location: chr11:113416867 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.49 · 11 PDB
Residue 176: a disulfide bond

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.Asn176Asp 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-asn176 (accessed [today's date]).

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