Is DRD3 p.Gln240= (c.720G>A) pathogenic?

DRD3 p.Gln240= (c.720G>A) is classified Benign in DRD3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-01-13). Common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele; Associated with tremor, hereditary essential, 1.

What condition is associated with DRD3 p.Gln240= (c.720G>A)?

DRD3 p.Gln240= (c.720G>A) is associated with tremor, hereditary essential, 1 (ClinVar).

DRD3 p.Gln240=

Q: How common is DRD3 p.Gln240= (c.720G>A) in the general population?

DRD3 p.Gln240= (c.720G>A) is common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.720G>A · rs2251177 · VCV342598

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

tremor, hereditary essential, 1

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 -0.42	GERP -3.5, phastCons 0.19
Overall
CADD	1.101	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 100% East Asian · 44,866/44,874 alleles

Filtering AF 99.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 99.8%

Overall 99.2% 1,599,599/1,613,062 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	100%	1
Finnishnot grpmax-eligible	100%	1
Ashkenazi Jewishnot grpmax-eligible	100%	1
East Asiangrpmax	100%	1
European (non-Finnish)	100%	1
Admixed American	99.1%	1
Middle Eastern	99%	1
Remaining individualsnot grpmax-eligible	98.9%	1
South Asian	97.5%	1
African / African-American	87.3%	1

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: DRD3
Protein: p.Gln240=
Coding: c.720G>A
MANE Select: NM_000796
dbSNP: rs2251177
Type: single nucleotide variant
Location: chr3:114139503 (GRCh38)
Gene constraint: LOEUF 0.604 · pLI 0.66 (gnomAD)
Structure: AlphaFold pLDDT 75.70 · 9 PDB

Full DRD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

tremor, hereditary essential, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DRD3 c.-105G>A Likely benign ★★ same condition
DRD3 c.-333G>A Benign ★★ same condition
DRD3 p.Ala17= Benign ★★ same condition
DRD3 p.Ala38Thr Likely benign ★★ same condition
DRD3 p.Gln329= Benign ★★ same condition
DRD3 p.Gly9Ser Benign/Likely benign ★★ same condition
DRD3 p.His359= Benign/Likely benign ★★ same condition
DRD3 p.Pro135His 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/drd3-p-gln240 (accessed [today's date]).

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