Is DRD2 p.His313= (c.939T>C) pathogenic?

DRD2 p.His313= (c.939T>C) is classified Benign in DRD2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-03). Common (popmax 70.6%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with dystonic disorder.

What condition is associated with DRD2 p.His313= (c.939T>C)?

DRD2 p.His313= (c.939T>C) is associated with dystonic disorder, schizophrenia (ClinVar).

DRD2 p.His313=

Q: How common is DRD2 p.His313= (c.939T>C) in the general population?

DRD2 p.His313= (c.939T>C) is common (popmax 70.6%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.939T>C · rs6275 · VCV256814

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 70.6%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

dystonic disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.81 · evaluated, not missing
Constraint at this position
Conservation	phyloP -12	GERP -4.1
Overall
CADD	0.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 70.6% European (non-Finnish) · 832,696/1,179,924 alleles

Filtering AF 70.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 70.4%

Overall 67.2% 1,083,808/1,613,622 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	71.1%	1
European (non-Finnish)grpmax	70.6%	1
Finnishnot grpmax-eligible	66.7%	1
Admixed American	65.8%	2
Remaining individualsnot grpmax-eligible	65.4%	2
Ashkenazi Jewishnot grpmax-eligible	65.1%	2
South Asian	63.1%	2
Middle Eastern	58.7%	2
East Asian	44.9%	2
African / African-American	36.2%	3

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.His313=
Coding: c.939T>C
MANE Select: NM_000795
dbSNP: rs6275
Type: single nucleotide variant
Location: chr11:113412755 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.49 · 11 PDB
Residue 313: the 'interaction with ppp1r9b' region; the 'disordered' region

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: schizophrenia

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-his313 (accessed [today's date]).

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