Is DRD3 p.His359= (c.1077C>T) pathogenic?

DRD3 p.His359= (c.1077C>T) is classified Benign/Likely benign in DRD3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-01). Low-frequency (popmax 1.34%, eas); Associated with tremor, hereditary essential, 1.

What condition is associated with DRD3 p.His359= (c.1077C>T)?

DRD3 p.His359= (c.1077C>T) is associated with tremor, hereditary essential, 1 (ClinVar).

How common is DRD3 p.His359= (c.1077C>T) in the general population?

DRD3 p.His359= (c.1077C>T) is low-frequency (popmax 1.34%, eas) (gnomAD).

DRD3 p.His359=

c.1077C>T · rs3732791 · VCV342595

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.34%, eas)

Conditions

tremor, hereditary essential, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.155	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -3.7	GERP -3.8
Overall
CADD	7.182	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.34% East Asian · 602/44,872 alleles

Filtering AF 1.25% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.22%

Overall 0.0976% 1,576/1,613,932 alleles · low-frequency exomes 1,441/1,461,646 · genomes 135/152,286 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	1.34%	75
South Asian	0.914%	109
Remaining individualsnot grpmax-eligible	0.131%	762
Admixed American	0.03%	3,333
Middle Eastern	0.0165%	6,062
African / African-American	0.0107%	9,379
European (non-Finnish)	0.0028%	35,755

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.His359=
Coding: c.1077C>T
MANE Select: NM_000796
dbSNP: rs3732791
Type: single nucleotide variant
Location: chr3:114128842 (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.Gln240= Benign ★★ same condition
DRD3 p.Gln329= Benign ★★ same condition
DRD3 p.Gly9Ser 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-his359 (accessed [today's date]).

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