Is DBH p.Gln513= (c.1539G>A) pathogenic?

DBH p.Gln513= (c.1539G>A) is classified Benign in DBH (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-08). Low-frequency (popmax 2.01%, afr); Associated with orthostatic hypotension 1.

What condition is associated with DBH p.Gln513= (c.1539G>A)?

DBH p.Gln513= (c.1539G>A) is associated with orthostatic hypotension 1 (ClinVar).

How common is DBH p.Gln513= (c.1539G>A) in the general population?

DBH p.Gln513= (c.1539G>A) is low-frequency (popmax 2.01%, afr) (gnomAD).

How is Dopamine beta-hydroxylase deficiency inherited?

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

DBH p.Gln513=

c.1539G>A · rs78516399 · VCV791717

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 2.01%, afr)

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 3.2	GERP 1.2, phastCons 1
Overall
CADD	7.352	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.01% African / African-American · 1,505/75,050 alleles

Filtering AF 1.92% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.89%

Overall 0.101% 1,636/1,612,950 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.01%	50
Remaining individualsnot grpmax-eligible	0.128%	781
Admixed American	0.06%	1,667
Middle Eastern	0.0495%	2,021
South Asian	0.0132%	7,589

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.Gln513=
Coding: c.1539G>A
MANE Select: NM_000787
dbSNP: rs78516399
Type: single nucleotide variant
Location: chr9:133656627 (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 513: a disulfide bond; an α-helix

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 p.Gln513Ter Likely pathogenic ★ same residue
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

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-gln513 (accessed [today's date]).

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