Is DBH p.His263Arg (c.788A>G) pathogenic?

DBH p.His263Arg (c.788A>G) is classified Uncertain significance in DBH (ClinVar, Single submitter, 1 submitter; last evaluated 2020-05-20). AlphaMissense: likely pathogenic (0.9892); Absent from gnomAD v4.1; Associated with orthostatic hypotension 1.

What condition is associated with DBH p.His263Arg (c.788A>G)?

DBH p.His263Arg (c.788A>G) is associated with orthostatic hypotension 1 (ClinVar).

How common is DBH p.His263Arg (c.788A>G) in the general population?

DBH p.His263Arg (c.788A>G) is absent from gnomAD v4.1 (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.His263Arg (c.788A>G)?

AlphaMissense predicts likely pathogenic (score 0.9892) — an in-silico prediction, not a clinical call.

DBH p.His263Arg

c.788A>G · rs2131285655 · VCV1060933

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9892 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

orthostatic hypotension 1

Computational evidence

Protein change
AlphaMissense	0.9892	likely pathogenic · top 2% in DBH
REVEL	0.827	moderately pathogenic-leaning
SaProt	LLR -11.57	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 11	GERP 1.3, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 22 kb · p 0.96 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DBH
Protein: p.His263Arg
Coding: c.788A>G
MANE Select: NM_000787
dbSNP: rs2131285655
Type: single nucleotide variant
Location: chr9:133643456 (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 263: a binding site; 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.His263= 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
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-his263arg (accessed [today's date]).

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