Is DRD3 p.Arg58Trp (c.172C>T) pathogenic?

DRD3 p.Arg58Trp (c.172C>T) is classified Uncertain significance in DRD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-27). AlphaMissense: ambiguous (0.4586); Ultra-rare (popmax 0.0165%, mid).

How common is DRD3 p.Arg58Trp (c.172C>T) in the general population?

DRD3 p.Arg58Trp (c.172C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about DRD3 p.Arg58Trp (c.172C>T)?

AlphaMissense predicts ambiguous (score 0.4586) — an in-silico prediction, not a clinical call.

DRD3 p.Arg58Trp

c.172C>T · rs376795590 · VCV2332247

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4586 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Computational evidence

Protein change
AlphaMissense	0.4586	ambiguous
REVEL	0.347	indeterminate
SaProt	LLR -12.34	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP -1.4, phastCons 0.96
Regional constraint	o/e 0.92	unconstrained · MANE · 43 kb · p 0.073 · regional, not allelic
Overall
CADD	24.4	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 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.0092% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0072%

Overall 0.00161% 26/1,614,058 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
African / African-American	0.016%	6,254
East Asian	0.00223%	44,866
Admixed American	0.00167%	60,016
Remaining individualsnot grpmax-eligible	0.0016%	62,494
European (non-Finnish)	0.000847%	117,999

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.Arg58Trp
Coding: c.172C>T
MANE Select: NM_000796
dbSNP: rs376795590
Type: single nucleotide variant
Location: chr3:114171821 (GRCh38)
Gene constraint: LOEUF 0.604 · pLI 0.66 (gnomAD)
Structure: AlphaFold pLDDT 75.70 · 9 PDB
Residue 58: 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-arg58trp (accessed [today's date]).

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