DRD3 p.His349=
c.1047T>C · rs139341493 · VCV726241
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.29%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.052 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.23 | acceptor loss, 22 bp away · masked 0 · deltas |
| Constraint at this position | ||
| Conservation | phyloP -0.71 | GERP -3.8 |
| Overall | ||
| CADD | 2.363 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.29%
Middle Eastern · 78/6,056 alleles
Filtering AF
1.06%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.973%
Overall
0.0659%
1,061/1,611,096 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 1.29% | 78 |
| Ashkenazi Jewishnot grpmax-eligible | 0.605% | 165 |
| Remaining individualsnot grpmax-eligible | 0.167% | 600 |
| South Asian | 0.0916% | 1,092 |
| Admixed American | 0.0791% | 1,265 |
| European (non-Finnish) | 0.0456% | 2,191 |
| African / African-American | 0.0254% | 3,942 |
| Finnishnot grpmax-eligible | 0.0219% | 4,569 |
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.His349=
- Coding
- c.1047T>C
- MANE Select
- NM_000796
- dbSNP
- rs139341493
- Type
- single nucleotide variant
- Location
- chr3:114128872 (GRCh38)
- Gene constraint
- LOEUF 0.604 · pLI 0.66 (gnomAD)
- Structure
- AlphaFold pLDDT 75.70 · 9 PDB
- Residue 349
- a binding site; an α-helix
Similar variants
- DRD3 c.-105G>A Likely benign ★★ same type
- DRD3 c.-333G>A Benign ★★ same type
- DRD3 p.Ala17= Benign ★★ same type
- DRD3 p.Ala38Thr Likely benign ★★ same type
- DRD3 p.Gln240= Benign ★★ same type
- DRD3 p.Gln329= Benign ★★ same type
- DRD3 p.Gly9Ser Benign/Likely benign ★★ same type
- DRD3 p.His359= Benign/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/drd3-p-his349 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown