Is DRD2 p.Ala410Thr (c.1228G>A) pathogenic?

DRD2 p.Ala410Thr (c.1228G>A) is classified Benign in DRD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-13). AlphaMissense: likely benign (0.1103); Rare (popmax 0.522%, amr); Associated with dystonic disorder.

What condition is associated with DRD2 p.Ala410Thr (c.1228G>A)?

DRD2 p.Ala410Thr (c.1228G>A) is associated with dystonic disorder (ClinVar).

How common is DRD2 p.Ala410Thr (c.1228G>A) in the general population?

DRD2 p.Ala410Thr (c.1228G>A) is rare (popmax 0.522%, amr) (gnomAD).

What do computational predictors say about DRD2 p.Ala410Thr (c.1228G>A)?

AlphaMissense predicts likely benign (score 0.1103) — an in-silico prediction, not a clinical call.

DRD2 p.Ala410Thr

c.1228G>A · rs758683320 · VCV238184

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1103 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.522%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

dystonic disorder

Computational evidence

Protein change
AlphaMissense	0.1103	likely benign
REVEL	0.27	benign-leaning
SaProt	LLR -6.14	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.49	unconstrained · MANE · 1,939 bp · p 3.2e-09 · regional, not allelic
Overall
CADD	28.7	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.522% Admixed American · 313/60,002 alleles

Filtering AF 0.474% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.455%

Overall 0.0206% 332/1,614,014 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.522%	192
Middle Eastern	0.0329%	3,042
Remaining individualsnot grpmax-eligible	0.0048%	20,830
European (non-Finnish)	0.00119%	84,287

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.Ala410Thr
Coding: c.1228G>A
MANE Select: NM_000795
dbSNP: rs758683320
Type: single nucleotide variant
Location: chr11:113410831 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.49 · 11 PDB
Residue 410: 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-ala410thr (accessed [today's date]).

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