Is DRD2 p.Val154Ile (c.460G>A) pathogenic?

DRD2 p.Val154Ile (c.460G>A) is classified Uncertain significance in DRD2 (ClinVar, Single submitter, 2 submitters; last evaluated 2026-01-05). AlphaMissense: likely benign (0.0715); Ultra-rare (popmax 0.0133%, afr); Associated with dystonic disorder.

What condition is associated with DRD2 p.Val154Ile (c.460G>A)?

DRD2 p.Val154Ile (c.460G>A) is associated with dystonic disorder, myoclonic dystonia 11 (ClinVar).

How common is DRD2 p.Val154Ile (c.460G>A) in the general population?

DRD2 p.Val154Ile (c.460G>A) is ultra-rare (popmax 0.0133%, afr) (gnomAD).

What do computational predictors say about DRD2 p.Val154Ile (c.460G>A)?

AlphaMissense predicts likely benign (score 0.0715) — an in-silico prediction, not a clinical call.

DRD2 p.Val154Ile

c.460G>A · rs104894220 · VCV16771

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0715 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

dystonic disorder

Computational evidence

Protein change
AlphaMissense	0.0715	likely benign
REVEL	0.324	indeterminate
SaProt	LLR -6.04	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -0.88, phastCons 0.98
Regional constraint	o/e 0.64	unconstrained · MANE · 9,057 bp · p 6.7e-09 · regional, not allelic
Overall
CADD	23.1	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% African / African-American · 10/74,940 alleles

Filtering AF 0.00723% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0055%

Overall 0.00297% 48/1,614,034 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0133%	7,494
Remaining individualsnot grpmax-eligible	0.008%	12,497
European (non-Finnish)	0.00254%	39,334
South Asian	0.0022%	45,534
Admixed American	0.00167%	59,998

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.Val154Ile
Coding: c.460G>A
MANE Select: NM_000795
dbSNP: rs104894220
Type: single nucleotide variant
Location: chr11:113416935 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.49 · 11 PDB
Residue 154: a disulfide bond; a UniProt-annotated variant site (found in patients with alcohol-responsive myoclonus-dystonia; uncertain significance; the mutation does not affect functional properties); 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

Also linked: myoclonic dystonia 11

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-val154ile (accessed [today's date]).

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