Is DBH p.Arg178Gln (c.533G>A) pathogenic?

DBH p.Arg178Gln (c.533G>A) is classified Benign in DBH (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-25). AlphaMissense: likely benign (0.0655); Low-frequency (popmax 2.02%, afr); Associated with orthostatic hypotension 1.

What condition is associated with DBH p.Arg178Gln (c.533G>A)?

DBH p.Arg178Gln (c.533G>A) is associated with orthostatic hypotension 1 (ClinVar).

How common is DBH p.Arg178Gln (c.533G>A) in the general population?

DBH p.Arg178Gln (c.533G>A) is low-frequency (popmax 2.02%, afr) (gnomAD).

How is Dopamine beta-hydroxylase deficiency inherited?

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

What do computational predictors say about DBH p.Arg178Gln (c.533G>A)?

AlphaMissense predicts likely benign (score 0.0655) — an in-silico prediction, not a clinical call.

DBH p.Arg178Gln

c.533G>A · rs76819676 · VCV365639

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0655 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.02%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

orthostatic hypotension 1

Computational evidence

Protein change
AlphaMissense	0.0655	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -4.10	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9	GERP -2.7
Regional constraint	o/e 1.00	unconstrained · MANE · 22 kb · p 0.96 · regional, not allelic
Overall
CADD	0.009	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.02% African / African-American · 1,516/75,020 alleles

Filtering AF 1.94% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9%

Overall 0.114% 1,833/1,613,936 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.02%	49
Admixed American	0.185%	541
Remaining individualsnot grpmax-eligible	0.165%	607
Middle Eastern	0.132%	756
South Asian	0.0143%	7,007
European (non-Finnish)	0.00686%	14,568
Finnishnot grpmax-eligible	0.00157%	63,880

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.Arg178Gln
Coding: c.533G>A
MANE Select: NM_000787
dbSNP: rs76819676
Type: single nucleotide variant
Location: chr9:133642253 (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 178: 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 p.Arg178Trp Uncertain significance ★ ⚠ same residue
DBH p.Arg178= Likely benign ★ 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

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-arg178gln (accessed [today's date]).

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