Is DBH p.Ile433= (c.1299C>T) pathogenic?

DBH p.Ile433= (c.1299C>T) is classified Likely benign in DBH (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-17). Rare (popmax 0.134%, eas); Associated with orthostatic hypotension 1.

What condition is associated with DBH p.Ile433= (c.1299C>T)?

DBH p.Ile433= (c.1299C>T) is associated with orthostatic hypotension 1 (ClinVar).

How common is DBH p.Ile433= (c.1299C>T) in the general population?

DBH p.Ile433= (c.1299C>T) is rare (popmax 0.134%, 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.Ile433=

c.1299C>T · rs368208047 · VCV791063

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.134%, eas)

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 -15	GERP -2.8
Overall
CADD	0.082	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.134% East Asian · 60/44,818 alleles

Filtering AF 0.107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0969%

Overall 0.00992% 160/1,613,320 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.134%	747
Admixed American	0.06%	1,666
Remaining individualsnot grpmax-eligible	0.00801%	12,492
African / African-American	0.00533%	18,753
European (non-Finnish)	0.00458%	21,849
South Asian	0.0011%	90,998

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.Ile433=
Coding: c.1299C>T
MANE Select: NM_000787
dbSNP: rs368208047
Type: single nucleotide variant
Location: chr9:133651741 (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 433: 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 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-ile433 (accessed [today's date]).

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