Is DRD3 p.Cys231Ser (c.691T>A) pathogenic?

DRD3 p.Cys231Ser (c.691T>A) is classified Likely benign in DRD3 (ClinVar, Single submitter, 2 submitters; last evaluated 2018-01-13). AlphaMissense: likely benign (0.1161); Rare (popmax 0.544%, afr); Associated with tremor, hereditary essential, 1.

What condition is associated with DRD3 p.Cys231Ser (c.691T>A)?

DRD3 p.Cys231Ser (c.691T>A) is associated with tremor, hereditary essential, 1 (ClinVar).

How common is DRD3 p.Cys231Ser (c.691T>A) in the general population?

DRD3 p.Cys231Ser (c.691T>A) is rare (popmax 0.544%, afr) (gnomAD).

What do computational predictors say about DRD3 p.Cys231Ser (c.691T>A)?

AlphaMissense predicts likely benign (score 0.1161) — an in-silico prediction, not a clinical call.

DRD3 p.Cys231Ser

c.691T>A · rs150042478 · VCV342599

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1161 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.544%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

tremor, hereditary essential, 1

Computational evidence

Protein change
AlphaMissense	0.1161	likely benign
REVEL	0.308	indeterminate
SaProt	LLR -5.21	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 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 43 kb · p 0.073 · regional, not allelic
Overall
CADD	17.85	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 0.544% African / African-American · 408/75,058 alleles

Filtering AF 0.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.483%

Overall 0.0277% 447/1,614,048 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.544%	184
Remaining individualsnot grpmax-eligible	0.0304%	3,289
Admixed American	0.025%	4,002
European (non-Finnish)	0.000424%	235,990

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: DRD3
Protein: p.Cys231Ser
Coding: c.691T>A
MANE Select: NM_000796
dbSNP: rs150042478
Type: single nucleotide variant
Location: chr3:114139532 (GRCh38)
Gene constraint: LOEUF 0.604 · pLI 0.66 (gnomAD)
Structure: AlphaFold pLDDT 75.70 · 9 PDB

Full DRD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

tremor, hereditary essential, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DRD3 c.-105G>A Likely benign ★★ same condition
DRD3 c.-333G>A Benign ★★ same condition
DRD3 p.Ala17= Benign ★★ same condition
DRD3 p.Ala38Thr Likely benign ★★ same condition
DRD3 p.Gln240= Benign ★★ same condition
DRD3 p.Gln329= Benign ★★ same condition
DRD3 p.Gly9Ser Benign/Likely benign ★★ same condition
DRD3 p.His359= Benign/Likely benign ★★ same condition

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/drd3-p-cys231ser (accessed [today's date]).

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