Is DBH p.Arg329Cys (c.985C>T) pathogenic?

DBH p.Arg329Cys (c.985C>T) is classified Likely benign in DBH (ClinVar, Single submitter, 2 submitters; last evaluated 2025-09-17). AlphaMissense: likely pathogenic (0.6208); Rare (popmax 0.185%, eas); Associated with orthostatic hypotension 1.

What condition is associated with DBH p.Arg329Cys (c.985C>T)?

DBH p.Arg329Cys (c.985C>T) is associated with orthostatic hypotension 1 (ClinVar).

How common is DBH p.Arg329Cys (c.985C>T) in the general population?

DBH p.Arg329Cys (c.985C>T) is rare (popmax 0.185%, eas) (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.Arg329Cys (c.985C>T)?

AlphaMissense predicts likely pathogenic (score 0.6208) — an in-silico prediction, not a clinical call.

DBH p.Arg329Cys

c.985C>T · rs201128036 · VCV773786

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6208 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.185%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

orthostatic hypotension 1

Computational evidence

Protein change
AlphaMissense	0.6208	likely pathogenic
REVEL	0.323	indeterminate
SaProt	LLR -12.59	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	Δ0.24	donor loss · deltas
Pangolin	Δ0.21	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.4	GERP 1.3, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 22 kb · p 0.96 · regional, not allelic
Overall
CADD	33.0	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 0.185% East Asian · 83/44,888 alleles

Filtering AF 0.153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.141%

Overall 0.00712% 115/1,614,182 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.185%	541
Remaining individualsnot grpmax-eligible	0.0128%	7,813
Admixed American	0.005%	20,011
European (non-Finnish)	0.00169%	59,001
African / African-American	0.00133%	75,050

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.Arg329Cys
Coding: c.985C>T
MANE Select: NM_000787
dbSNP: rs201128036
Type: single nucleotide variant
Location: chr9:133644281 (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 329: a disulfide bond; a β-strand

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.Arg329His 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-arg329cys (accessed [today's date]).

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