Is DRD5 p.Arg72= (c.216C>G) pathogenic?

DRD5 p.Arg72= (c.216C>G) is classified Likely benign in DRD5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-02-19). Ultra-rare (popmax 0.012%, afr); Associated with DRD5-related disorder.

What condition is associated with DRD5 p.Arg72= (c.216C>G)?

DRD5 p.Arg72= (c.216C>G) is associated with DRD5-related disorder (ClinVar).

How common is DRD5 p.Arg72= (c.216C>G) in the general population?

DRD5 p.Arg72= (c.216C>G) is ultra-rare (popmax 0.012%, afr) (gnomAD).

DRD5 p.Arg72=

c.216C>G · rs746485772 · VCV3058787

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Conditions

DRD5-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.5	GERP -3.7
Overall
CADD	4.796	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.012% African / African-American · 9/74,938 alleles

Filtering AF 0.00623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00467%

Overall 0.000744% 12/1,613,442 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,326
Admixed American	0.00167%	59,998
European (non-Finnish)	0.00017%	589,922

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: DRD5
Protein: p.Arg72=
Coding: c.216C>G
MANE Select: NM_000798
dbSNP: rs746485772
Type: single nucleotide variant
Location: chr4:9782245 (GRCh38)
Gene constraint: LOEUF 1.851 · pLI 0.09 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.45 · 1 PDB
Residue 72: an α-helix

Full DRD5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DRD5-related disorder

Similar variants

DRD5 p.Val115Ile Uncertain significance ★ ⚠ same condition
DRD5 c.-5C>G Likely benign same condition
DRD5 p.Asp211Asn Likely benign same condition
DRD5 p.Cys62Ter Likely benign same condition
DRD5 p.His268Gln Benign same condition
DRD5 p.Val59Met Uncertain significance ★★ ⚠ same type
DRD5 c.-226G>C Benign ★★ same type
DRD5 c.*178G>T 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/drd5-p-arg72 (accessed [today's date]).

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