Is DRD2 p.Pro310Ser (c.928C>T) pathogenic?

DRD2 p.Pro310Ser (c.928C>T) is classified Conflicting classifications of pathogenicity in DRD2 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.0645); Low-frequency (popmax 2.76%, mid); Associated with DRD2-associated Dystonia.

What condition is associated with DRD2 p.Pro310Ser (c.928C>T)?

DRD2 p.Pro310Ser (c.928C>T) is associated with DRD2-associated Dystonia, dystonic disorder (ClinVar).

How common is DRD2 p.Pro310Ser (c.928C>T) in the general population?

DRD2 p.Pro310Ser (c.928C>T) is low-frequency (popmax 2.76%, mid) (gnomAD).

What do computational predictors say about DRD2 p.Pro310Ser (c.928C>T)?

AlphaMissense predicts likely benign (score 0.0645) — an in-silico prediction, not a clinical call.

DRD2 p.Pro310Ser

c.928C>T · rs1800496 · VCV256812

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0645 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.76%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DRD2-associated Dystonia

Computational evidence

Protein change
AlphaMissense	0.0645	likely benign
REVEL	0.053	moderately benign-leaning
SaProt	LLR -5.64	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 4.9	GERP -2.4, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 2,833 bp · p 0.35 · regional, not allelic
Overall
CADD	14.97	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 2.76% Middle Eastern · 167/6,058 alleles

Filtering AF 2.42% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.28%

Overall 0.109% 1,751/1,613,788 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	2.76%	36
Ashkenazi Jewishnot grpmax-eligible	1.66%	60
Remaining individualsnot grpmax-eligible	0.246%	406
South Asian	0.123%	813
Admixed American	0.11%	909
European (non-Finnish)	0.0616%	1,623
African / African-American	0.04%	2,501
Finnishnot grpmax-eligible	0.00625%	16,008

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.Pro310Ser
Coding: c.928C>T
MANE Select: NM_000795
dbSNP: rs1800496
Type: single nucleotide variant
Location: chr11:113412766 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.49 · 11 PDB
Residue 310: the 'interaction with ppp1r9b' region; the 'disordered' region; a UniProt-annotated variant site (in)

Full DRD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DRD2-associated Dystonia

Also linked: dystonic disorder

Similar variants

DRD2 p.Pro310= Benign ★ same residue
DRD2 p.Pro310Leu 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

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-pro310ser (accessed [today's date]).

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