Is DRD3 p.Arg391Gln (c.1172G>A) pathogenic?

DRD3 p.Arg391Gln (c.1172G>A) is classified Uncertain significance in DRD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-08). AlphaMissense: ambiguous (0.4127); Ultra-rare (popmax 0.0305%, amr).

How common is DRD3 p.Arg391Gln (c.1172G>A) in the general population?

DRD3 p.Arg391Gln (c.1172G>A) is ultra-rare (popmax 0.0305%, amr) (gnomAD).

What do computational predictors say about DRD3 p.Arg391Gln (c.1172G>A)?

AlphaMissense predicts ambiguous (score 0.4127) — an in-silico prediction, not a clinical call.

DRD3 p.Arg391Gln

c.1172G>A · VCV3505230

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4127 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0305%, amr)

Computational evidence

Protein change
AlphaMissense	0.4127	ambiguous
REVEL	0.527	indeterminate
SaProt	LLR -10.14	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 43 kb · p 0.073 · regional, not allelic
Overall
CADD	32.0	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 0.0305% Admixed American · 18/59,102 alleles

Filtering AF 0.0197% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0162%

Overall 0.00211% 34/1,608,130 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0305%	3,283
South Asian	0.00777%	12,878
East Asian	0.00447%	22,396
African / African-American	0.00268%	37,335
European (non-Finnish)	0.000425%	235,413

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.Arg391Gln
Coding: c.1172G>A
MANE Select: NM_000796
Type: single nucleotide variant
Location: chr3:114128747 (GRCh38)
Gene constraint: LOEUF 0.604 · pLI 0.66 (gnomAD)
Structure: AlphaFold pLDDT 75.70 · 9 PDB
Residue 391: an α-helix

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

Similar variants

DRD3 c.-105G>A Likely benign ★★ same type
DRD3 c.-333G>A Benign ★★ same type
DRD3 p.Ala17= Benign ★★ same type
DRD3 p.Ala38Thr Likely benign ★★ same type
DRD3 p.Gln240= Benign ★★ same type
DRD3 p.Gln329= Benign ★★ same type
DRD3 p.Gly9Ser Benign/Likely benign ★★ same type
DRD3 p.His349= Likely benign ★★ same type

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-arg391gln (accessed [today's date]).

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