Is DBH p.Ser402= (c.1206C>T) pathogenic?

DBH p.Ser402= (c.1206C>T) is classified Benign/Likely benign in DBH (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-30). Low-frequency (popmax 1.35%, afr); Associated with orthostatic hypotension 1.

What condition is associated with DBH p.Ser402= (c.1206C>T)?

DBH p.Ser402= (c.1206C>T) is associated with orthostatic hypotension 1 (ClinVar).

How common is DBH p.Ser402= (c.1206C>T) in the general population?

DBH p.Ser402= (c.1206C>T) is low-frequency (popmax 1.35%, 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.Ser402=

c.1206C>T · rs143743431 · VCV786393

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.35%, afr)

Conditions

orthostatic hypotension 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.42 · evaluated, not missing
Constraint at this position
Conservation	phyloP -16	GERP -2.8
Overall
CADD	0.027	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.35% African / African-American · 1,012/75,054 alleles

Filtering AF 1.28% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.25%

Overall 0.0734% 1,184/1,613,742 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.35%	74
Middle Eastern	0.117%	854
Remaining individualsnot grpmax-eligible	0.112%	893
Admixed American	0.085%	1,177
East Asian	0.00891%	11,220
South Asian	0.00439%	22,768
European (non-Finnish)	0.00305%	32,778

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.Ser402=
Coding: c.1206C>T
MANE Select: NM_000787
dbSNP: rs143743431
Type: single nucleotide variant
Location: chr9:133651648 (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 402: 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.Ser402Gly Uncertain significance ★ same residue
DBH p.Ser402Cys 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

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-ser402 (accessed [today's date]).

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