Is DRD2 p.Ser419= (c.1257C>T) pathogenic?

DRD2 p.Ser419= (c.1257C>T) is classified Likely benign in DRD2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-23). Rare (popmax 0.197%, mid); Associated with dystonic disorder.

What condition is associated with DRD2 p.Ser419= (c.1257C>T)?

DRD2 p.Ser419= (c.1257C>T) is associated with dystonic disorder (ClinVar).

How common is DRD2 p.Ser419= (c.1257C>T) in the general population?

DRD2 p.Ser419= (c.1257C>T) is rare (popmax 0.197%, mid) (gnomAD).

DRD2 p.Ser419=

c.1257C>T · rs79932566 · VCV1644209

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.197%, mid)

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 0.77	GERP -3, phastCons 1
Overall
CADD	12.06	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.197% Middle Eastern · 12/6,084 alleles

Filtering AF 0.114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0892%

Overall 0.0209% 337/1,612,974 alleles · rare exomes 300/1,461,886 · genomes 37/151,088 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.197%	507
Remaining individualsnot grpmax-eligible	0.0416%	2,403
Admixed American	0.0384%	2,605
European (non-Finnish)	0.0214%	4,663
African / African-American	0.0201%	4,967
Ashkenazi Jewishnot grpmax-eligible	0.0169%	5,919
East Asian	0.00223%	44,836
Finnishnot grpmax-eligible	0.00156%	64,002
South Asian	0.0011%	91,006

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.Ser419=
Coding: c.1257C>T
MANE Select: NM_000795
dbSNP: rs79932566
Type: single nucleotide variant
Location: chr11:113410802 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.49 · 11 PDB
Residue 419: 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-ser419 (accessed [today's date]).

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