Is DRD2 p.Ala64Val (c.191C>T) pathogenic?

DRD2 p.Ala64Val (c.191C>T) is classified Conflicting classifications of pathogenicity in DRD2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-07-24). AlphaMissense: ambiguous (0.484); Ultra-rare (popmax 0.0757%, eas); Associated with dystonic disorder.

What condition is associated with DRD2 p.Ala64Val (c.191C>T)?

DRD2 p.Ala64Val (c.191C>T) is associated with dystonic disorder (ClinVar).

How common is DRD2 p.Ala64Val (c.191C>T) in the general population?

DRD2 p.Ala64Val (c.191C>T) is ultra-rare (popmax 0.0757%, eas) (gnomAD).

What do computational predictors say about DRD2 p.Ala64Val (c.191C>T)?

AlphaMissense predicts ambiguous (score 0.484) — an in-silico prediction, not a clinical call.

DRD2 p.Ala64Val

c.191C>T · rs201137518 · VCV696532

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.484 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0757%, eas)

Conditions

dystonic disorder

Computational evidence

Protein change
AlphaMissense	0.484	ambiguous
REVEL	0.556	indeterminate
SaProt	LLR -7.14	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.9, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 9,057 bp · p 6.7e-09 · regional, not allelic
Overall
CADD	33.0	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 0.0757% East Asian · 34/44,886 alleles

Filtering AF 0.0557% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0488%

Overall 0.00737% 119/1,614,246 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0757%	1,320
Remaining individualsnot grpmax-eligible	0.056%	1,786
Admixed American	0.055%	1,819
Middle Eastern	0.0165%	6,062
African / African-American	0.00533%	18,765
South Asian	0.00439%	22,772
European (non-Finnish)	0.000678%	147,507

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.Ala64Val
Coding: c.191C>T
MANE Select: NM_000795
dbSNP: rs201137518
Type: single nucleotide variant
Location: chr11:113424461 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.49 · 11 PDB
Residue 64: 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-ala64val (accessed [today's date]).

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