Is DRD5 p.Arg155Cys (c.463C>T) pathogenic?

DRD5 p.Arg155Cys (c.463C>T) is classified Uncertain significance in DRD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-05). AlphaMissense: likely benign (0.0901); Very rare (popmax 0.0011%, sas).

How common is DRD5 p.Arg155Cys (c.463C>T) in the general population?

DRD5 p.Arg155Cys (c.463C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about DRD5 p.Arg155Cys (c.463C>T)?

AlphaMissense predicts likely benign (score 0.0901) — an in-silico prediction, not a clinical call.

DRD5 p.Arg155Cys

c.463C>T · rs1220933467 · VCV3085798

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0901 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0901	likely benign
REVEL	0.319	indeterminate
SaProt	LLR -10.41	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.58	GERP -3.4
Regional constraint	o/e 1.15	unconstrained · MANE · 1,430 bp · p 9.4e-05 · regional, not allelic
Overall
CADD	23.2	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 0.0011% South Asian · 1/91,074 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000616% 9/1,461,638 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0064%	15,622
South Asiangrpmax	0.0011%	91,074
European (non-Finnish)	0.000339%	294,962

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg155Cys
Coding: c.463C>T
MANE Select: NM_000798
dbSNP: rs1220933467
Type: single nucleotide variant
Location: chr4:9782492 (GRCh38)
Gene constraint: LOEUF 1.851 · pLI 0.09 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.45 · 1 PDB
Residue 155: a disulfide bond; an α-helix

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

Similar variants

DRD5 p.Arg155His Uncertain significance ★ ⚠ same residue
DRD5 p.Val59Met Uncertain significance ★★ ⚠ same type
DRD5 c.-226G>C Benign ★★ same type
DRD5 c.*178G>T Benign ★★ same type
DRD5 p.Leu88Phe Benign ★★ ⚠ same type
DRD5 c.*47T>C Conflicting classifications of pathogenicity ★ same type
DRD5 p.Ala10Val Uncertain significance ★ ⚠ same type
DRD5 p.Ala111Glu 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/drd5-p-arg155cys (accessed [today's date]).

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