Is DRD4 p.Arg63Cys (c.187C>T) pathogenic?

DRD4 p.Arg63Cys (c.187C>T) is classified Uncertain significance in DRD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-10). AlphaMissense: ambiguous (0.4497); Ultra-rare (popmax 0.0136%, afr).

How common is DRD4 p.Arg63Cys (c.187C>T) in the general population?

DRD4 p.Arg63Cys (c.187C>T) is ultra-rare (popmax 0.0136%, afr) (gnomAD).

What do computational predictors say about DRD4 p.Arg63Cys (c.187C>T)?

AlphaMissense predicts ambiguous (score 0.4497) — an in-silico prediction, not a clinical call.

DRD4 p.Arg63Cys

c.187C>T · rs571899363 · VCV2472191

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4497 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0136%, afr)

Computational evidence

Protein change
AlphaMissense	0.4497	ambiguous
REVEL	0.39	indeterminate
SaProt	LLR -12.53	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP 0.029, phastCons 1
Regional constraint	o/e 1.44	unconstrained · MANE · 3,295 bp · p 6.5e-29 · regional, not allelic
Overall
CADD	26.3	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 0.0136% African / African-American · 10/73,684 alleles

Filtering AF 0.00734% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00558%

Overall 0.0011% 17/1,548,400 alleles · ultra-rare exomes 7/1,396,110 · genomes 10/152,290 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0136%	7,368
South Asian	0.00473%	21,154
European (non-Finnish)	0.00026%	384,249

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: DRD4
Protein: p.Arg63Cys
Coding: c.187C>T
MANE Select: NM_000797
dbSNP: rs571899363
Type: single nucleotide variant
Location: chr11:637491 (GRCh38)
Gene constraint: LOEUF 1.952 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.06 · 2 PDB
Residue 63: an α-helix

Full DRD4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DRD4 p.Asn309Asp Uncertain significance ★★ ⚠ same type
DRD4 p.Ser308Pro Uncertain significance ★★ ⚠ same type
DRD4 p.Ala335Gly Benign ★★ same type
DRD4 p.Gly11Arg Benign ★★ same type
DRD4 p.Leu83= Likely benign ★★ same type
DRD4 p.Pro244= Likely benign ★★ same type
DRD4 p.Pro248= Likely benign ★★ same type
DRD4 p.Val398= 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/drd4-p-arg63cys (accessed [today's date]).

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