Is DRD3 p.Trp370Cys (c.1110G>T) pathogenic?

DRD3 p.Trp370Cys (c.1110G>T) is classified Uncertain significance in DRD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-21). AlphaMissense: likely pathogenic (0.9923); Absent from gnomAD v4.1; Associated with DRD3-related disorder.

What condition is associated with DRD3 p.Trp370Cys (c.1110G>T)?

DRD3 p.Trp370Cys (c.1110G>T) is associated with DRD3-related disorder (ClinVar).

How common is DRD3 p.Trp370Cys (c.1110G>T) in the general population?

DRD3 p.Trp370Cys (c.1110G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DRD3 p.Trp370Cys (c.1110G>T)?

AlphaMissense predicts likely pathogenic (score 0.9923) — an in-silico prediction, not a clinical call.

DRD3 p.Trp370Cys

c.1110G>T · rs2107825397 · VCV2633497

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9923 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DRD3-related disorder

Computational evidence

Protein change
AlphaMissense	0.9923	likely pathogenic · top 6% in DRD3
REVEL	0.846	moderately pathogenic-leaning
SaProt	LLR -13.05	damaging
⇒ AlphaMissense, REVEL and SaProt all call this 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

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DRD3
Protein: p.Trp370Cys
Coding: c.1110G>T
MANE Select: NM_000796
dbSNP: rs2107825397
Type: single nucleotide variant
Location: chr3:114128809 (GRCh38)
Gene constraint: LOEUF 0.604 · pLI 0.66 (gnomAD)
Structure: AlphaFold pLDDT 75.70 · 9 PDB
Residue 370: an α-helix

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

Disease context

DRD3-related disorder

Similar variants

DRD3 p.Met52Thr Conflicting classifications of pathogenicity ★ ⚠ same condition
DRD3 p.Ala38= Likely benign same condition
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

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-trp370cys (accessed [today's date]).

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