Is DBH p.Arg602Ter (c.1804C>T) pathogenic?

DBH p.Arg602Ter (c.1804C>T) is classified Uncertain significance in DBH (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-15). Very rare (popmax 0.00669%, eas); Associated with orthostatic hypotension 1.

What condition is associated with DBH p.Arg602Ter (c.1804C>T)?

DBH p.Arg602Ter (c.1804C>T) is associated with orthostatic hypotension 1 (ClinVar).

How common is DBH p.Arg602Ter (c.1804C>T) in the general population?

DBH p.Arg602Ter (c.1804C>T) is very rare (popmax 0.00669%, eas) (gnomAD).

How is Dopamine beta-hydroxylase deficiency inherited?

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

DBH p.Arg602Ter

c.1804C>T · rs775827929 · VCV449010

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Conditions

orthostatic hypotension 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (12 of 12) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2	GERP 1.1, phastCons 0.006
Overall
CADD	48.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00669% East Asian · 3/44,866 alleles

Filtering AF 0.00207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00183%

Overall 0.00273% 44/1,613,622 alleles · very rare exomes 36/1,461,536 · genomes 8/152,086 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,955
African / African-American	0.00534%	18,722
Remaining individualsnot grpmax-eligible	0.0048%	20,825
European (non-Finnish)	0.00288%	34,701

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.Arg602Ter
Coding: c.1804C>T
MANE Select: NM_000787
dbSNP: rs775827929
Type: single nucleotide variant
Location: chr9:133658397 (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 602: the 'disordered' region

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.Arg602Gln Uncertain significance ★ ⚠ 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-arg602ter (accessed [today's date]).

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