Is DRD3 p.Val195Ala (c.584T>C) pathogenic?

DRD3 p.Val195Ala (c.584T>C) is classified Uncertain significance in DRD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-20). AlphaMissense: likely benign (0.2586); Absent from gnomAD v4.1.

How common is DRD3 p.Val195Ala (c.584T>C) in the general population?

DRD3 p.Val195Ala (c.584T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DRD3 p.Val195Ala (c.584T>C)?

AlphaMissense predicts likely benign (score 0.2586) — an in-silico prediction, not a clinical call.

DRD3 p.Val195Ala

c.584T>C · VCV4244790

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2586 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2586	likely benign
REVEL	0.205	benign-leaning
SaProt	LLR -5.32	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 43 kb · p 0.073 · regional, not allelic
Overall
CADD	22.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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.Val195Ala
Coding: c.584T>C
MANE Select: NM_000796
Type: single nucleotide variant
Location: chr3:114139639 (GRCh38)
Gene constraint: LOEUF 0.604 · pLI 0.66 (gnomAD)
Structure: AlphaFold pLDDT 75.70 · 9 PDB
Residue 195: 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-val195ala (accessed [today's date]).

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