Is DBH p.Glu162= (c.486A>G) pathogenic?

DBH p.Glu162= (c.486A>G) is classified Benign in DBH (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-04). Common (popmax 66.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with orthostatic hypotension 1.

What condition is associated with DBH p.Glu162= (c.486A>G)?

DBH p.Glu162= (c.486A>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.Glu162=

Q: How common is DBH p.Glu162= (c.486A>G) in the general population?

DBH p.Glu162= (c.486A>G) is common (popmax 66.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.486A>G · rs1108580 · VCV217758

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 66.9%, afr) — 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 8.4	GERP 0.022, phastCons 1
Overall
CADD	12.68	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 66.9% African / African-American · 50,166/74,974 alleles

Filtering AF 66.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 66.2%

Overall 51.6% 832,771/1,612,950 alleles · common exomes 751,787/1,460,888 · genomes 80,984/152,062 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	66.9%	1
European (non-Finnish)	54.8%	2
Finnishnot grpmax-eligible	50.3%	2
Remaining individualsnot grpmax-eligible	49%	2
Ashkenazi Jewishnot grpmax-eligible	46.1%	2
Middle Eastern	43.8%	2
South Asian	35.3%	3
Amishnot grpmax-eligible	33.7%	3
Admixed American	32.4%	3
East Asian	13.3%	7

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.Glu162=
Coding: c.486A>G
MANE Select: NM_000787
dbSNP: rs1108580
Type: single nucleotide variant
Location: chr9:133639992 (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 162: the domon domain

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-glu162 (accessed [today's date]).

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