Is DBH p.Thr470= (c.1410A>G) pathogenic?

DBH p.Thr470= (c.1410A>G) is classified Benign in DBH (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Common (popmax 90.4%, eas) — too common for a highly-penetrant pathogenic allele; Associated with orthostatic hypotension 1.

What condition is associated with DBH p.Thr470= (c.1410A>G)?

DBH p.Thr470= (c.1410A>G) is associated with orthostatic hypotension 1 (ClinVar).

How is Dopamine beta-hydroxylase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

DBH p.Thr470=

Q: How common is DBH p.Thr470= (c.1410A>G) in the general population?

DBH p.Thr470= (c.1410A>G) is common (popmax 90.4%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1410A>G · rs77905 · VCV365661

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 90.4%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

orthostatic hypotension 1

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 -10	GERP -2.7
Overall
CADD	0.127	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 90.4% East Asian · 40,534/44,824 alleles

Filtering AF 89.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 89.4%

Overall 52.7% 850,036/1,612,202 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	90.4%	1
Amishnot grpmax-eligible	69.6%	1
Admixed American	66.6%	2
African / African-American	57.3%	2
Middle Eastern	55.1%	2
South Asian	53.6%	2
Remaining individualsnot grpmax-eligible	52.9%	2
European (non-Finnish)	50.6%	2
Finnishnot grpmax-eligible	48.3%	2
Ashkenazi Jewishnot grpmax-eligible	47.1%	2

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.Thr470=
Coding: c.1410A>G
MANE Select: NM_000787
dbSNP: rs77905
Type: single nucleotide variant
Location: chr9:133652975 (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 470: a disulfide bond

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

Disease context

orthostatic hypotension 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Dopamine beta-hydroxylase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy, Neonatal

Similar variants

DBH c.339+2T>C Pathogenic ★★ same condition
DBH c.1024+6C>T Uncertain significance ★★ same condition
DBH c.486+15C>T Uncertain significance ★★ same condition
DBH c.*393C>T Uncertain significance ★★ same condition
DBH p.Ala113Ser Uncertain significance ★★ ⚠ same condition
DBH p.Ala259Val Uncertain significance ★★ ⚠ same condition
DBH p.Ala383Val Uncertain significance ★★ ⚠ same condition
DBH p.Ala506Thr Uncertain significance ★★ ⚠ 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/dbh-p-thr470 (accessed [today's date]).

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