Is DRD2 p.Val200Met (c.598G>A) pathogenic?

DRD2 p.Val200Met (c.598G>A) is classified Uncertain significance in DRD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-07). AlphaMissense: ambiguous (0.351); Ultra-rare (popmax 0.0446%, eas).

How common is DRD2 p.Val200Met (c.598G>A) in the general population?

DRD2 p.Val200Met (c.598G>A) is ultra-rare (popmax 0.0446%, eas) (gnomAD).

What do computational predictors say about DRD2 p.Val200Met (c.598G>A)?

AlphaMissense predicts ambiguous (score 0.351) — an in-silico prediction, not a clinical call.

DRD2 p.Val200Met

c.598G>A · rs138509142 · VCV2525453

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.351 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0446%, eas)

Computational evidence

Protein change
AlphaMissense	0.351	ambiguous
REVEL	0.493	indeterminate
SaProt	LLR -9.22	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 0.33, phastCons 1
Regional constraint	o/e 0.21	constrained · MANE · 89 bp · p 8.4e-07 · regional, not allelic
Overall
CADD	29.8	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 0.0446% East Asian · 20/44,868 alleles

Filtering AF 0.0295% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0246%

Overall 0.00582% 94/1,614,008 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0446%	2,243
Admixed American	0.015%	6,668
African / African-American	0.00667%	14,998
Remaining individualsnot grpmax-eligible	0.0064%	15,624
European (non-Finnish)	0.00466%	21,455
South Asian	0.0011%	91,062

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: DRD2
Protein: p.Val200Met
Coding: c.598G>A
MANE Select: NM_000795
dbSNP: rs138509142
Type: single nucleotide variant
Location: chr11:113415546 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.49 · 11 PDB
Residue 200: an α-helix

Full DRD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DRD2 p.Arg274Gln Uncertain significance ★★ ⚠ same type
DRD2 p.Gln366Lys Uncertain significance ★★ ⚠ same type
DRD2 p.Glu99Lys Uncertain significance ★★ ⚠ same type
DRD2 p.Gly261Arg Uncertain significance ★★ ⚠ same type
DRD2 p.His316Pro Uncertain significance ★★ ⚠ same type
DRD2 p.Ile431Thr Uncertain significance ★★ ⚠ same type
DRD2 p.Pro300His Uncertain significance ★★ ⚠ same type
DRD2 p.Val223Ile Uncertain significance ★★ ⚠ 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/drd2-p-val200met (accessed [today's date]).

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