DRD4 p.Leu83=
c.249C>T · rs149808759 · VCV752181
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0426%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4.3 | GERP -4.4 |
| Overall | ||
| CADD | 2.637 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0426%
East Asian · 18/42,228 alleles
Filtering AF
0.0345%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0333%
Overall
0.0337%
526/1,561,160 alleles · ultra-rare
exomes 488/1,408,870 · genomes 38/152,290 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0426% | 2,346 |
| European (non-Finnish) | 0.0374% | 2,674 |
| Remaining individualsnot grpmax-eligible | 0.0362% | 2,760 |
| South Asian | 0.0317% | 3,158 |
| Admixed American | 0.0284% | 3,526 |
| African / African-American | 0.0135% | 7,399 |
| Finnishnot grpmax-eligible | 0.00191% | 52,404 |
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
- DRD4
- Protein
- p.Leu83=
- Coding
- c.249C>T
- MANE Select
- NM_000797
- dbSNP
- rs149808759
- Type
- single nucleotide variant
- Location
- chr11:637553 (GRCh38)
- Gene constraint
- LOEUF 1.952 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.06 · 2 PDB
- Residue 83
- an α-helix
Similar variants
- DRD4 p.Asn309Asp Uncertain significance ★★ ⚠ same type
- DRD4 p.Ser308Pro Uncertain significance ★★ ⚠ same type
- DRD4 p.Ala335Gly Benign ★★ same type
- DRD4 p.Gly11Arg Benign ★★ same type
- DRD4 p.Pro244= Likely benign ★★ same type
- DRD4 p.Pro248= Likely benign ★★ same type
- DRD4 p.Val398= Likely benign ★★ same type
- DRD4 p.Val74= 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/drd4-p-leu83 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown