Is DRD3 p.Ala38Thr (c.112G>A) pathogenic?

DRD3 p.Ala38Thr (c.112G>A) is classified Likely benign in DRD3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-01-13). AlphaMissense: likely benign (0.0861); Low-frequency (popmax 1.83%, eas); Associated with tremor, hereditary essential, 1.

What condition is associated with DRD3 p.Ala38Thr (c.112G>A)?

DRD3 p.Ala38Thr (c.112G>A) is associated with tremor, hereditary essential, 1 (ClinVar).

How common is DRD3 p.Ala38Thr (c.112G>A) in the general population?

DRD3 p.Ala38Thr (c.112G>A) is low-frequency (popmax 1.83%, eas) (gnomAD).

What do computational predictors say about DRD3 p.Ala38Thr (c.112G>A)?

AlphaMissense predicts likely benign (score 0.0861) — an in-silico prediction, not a clinical call.

DRD3 p.Ala38Thr

c.112G>A · rs138354054 · VCV899697

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0861 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.83%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

tremor, hereditary essential, 1

Computational evidence

Protein change
AlphaMissense	0.0861	likely benign
REVEL	0.071	moderately benign-leaning
SaProt	LLR -7.30	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.26	GERP -1
Regional constraint	o/e 0.92	unconstrained · MANE · 43 kb · p 0.073 · regional, not allelic
Overall
CADD	14.02	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 1.83% East Asian · 820/44,814 alleles

Filtering AF 1.73% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.68%

Overall 0.0563% 909/1,613,238 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.83%	55
Remaining individualsnot grpmax-eligible	0.048%	2,082
South Asian	0.0165%	6,059
Admixed American	0.0117%	8,563
African / African-American	0.0107%	9,376
European (non-Finnish)	0.00246%	40,676

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.Ala38Thr
Coding: c.112G>A
MANE Select: NM_000796
dbSNP: rs138354054
Type: single nucleotide variant
Location: chr3:114171881 (GRCh38)
Gene constraint: LOEUF 0.604 · pLI 0.66 (gnomAD)
Structure: AlphaFold pLDDT 75.70 · 9 PDB
Residue 38: an α-helix

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 p.Ala38Val Uncertain significance ★ same residue
DRD3 p.Ala38= Likely benign same residue
DRD3 c.-105G>A Likely benign ★★ same condition
DRD3 c.-333G>A Benign ★★ same condition
DRD3 p.Ala17= Benign ★★ same condition
DRD3 p.Gln240= Benign ★★ same condition
DRD3 p.Gln329= Benign ★★ same condition
DRD3 p.Gly9Ser 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-ala38thr (accessed [today's date]).

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