DBH p.Lys82=
c.246G>A · VCV4905373
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00169%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.9 | GERP 0.41, phastCons 0.98 |
| Overall | ||
| CADD | 1.732 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00169%
European (non-Finnish) · 20/1,180,018 alleles
Filtering AF
0.00111%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0009%
Overall
0.00144%
21/1,461,260 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00169% | 59,001 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,506 |
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
- DBH
- Protein
- p.Lys82=
- Coding
- c.246G>A
- MANE Select
- NM_000787
- Type
- single nucleotide variant
- Location
- chr9:133636617 (GRCh38)
- Gene constraint
- LOEUF 0.936 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 90.58 · 1 PDB
- Residue 82
- the domon domain
Similar variants
- DBH p.Lys82Arg Uncertain significance ★ ⚠ same residue
- DBH p.Lys82Glu Uncertain significance ★ ⚠ same residue
- DBH c.339+2T>C Pathogenic ★★ same type
- DBH c.1024+6C>T Uncertain significance ★★ same type
- DBH c.486+15C>T Uncertain significance ★★ same type
- DBH c.*393C>T Uncertain significance ★★ same type
- DBH p.Ala113Ser Uncertain significance ★★ ⚠ same type
- DBH p.Ala259Val 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/dbh-p-lys82 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown