Is DRD2 p.Val53Met (c.157G>A) pathogenic?

DRD2 p.Val53Met (c.157G>A) is classified Uncertain significance in DRD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-24). AlphaMissense: likely benign (0.3013); Very rare (popmax 0.00246%, nfe).

How common is DRD2 p.Val53Met (c.157G>A) in the general population?

DRD2 p.Val53Met (c.157G>A) is very rare (popmax 0.00246%, nfe) (gnomAD).

What do computational predictors say about DRD2 p.Val53Met (c.157G>A)?

AlphaMissense predicts likely benign (score 0.3013) — an in-silico prediction, not a clinical call.

DRD2 p.Val53Met

c.157G>A · rs200010436 · VCV2296407

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3013 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00246%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3013	likely benign
REVEL	0.346	indeterminate
SaProt	LLR -9.07	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 0.69, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 9,057 bp · p 6.7e-09 · regional, not allelic
Overall
CADD	31.0	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

Grpmax group 0.00246% European (non-Finnish) · 29/1,180,046 alleles

Filtering AF 0.00172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.00192% 31/1,614,096 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00246%	40,691
Admixed American	0.00167%	60,010
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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.Val53Met
Coding: c.157G>A
MANE Select: NM_000795
dbSNP: rs200010436
Type: single nucleotide variant
Location: chr11:113424495 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.49 · 11 PDB
Residue 53: 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-val53met (accessed [today's date]).

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