Is DBH p.Glu341= (c.1023A>G) pathogenic?

DBH p.Glu341= (c.1023A>G) is classified Uncertain significance in DBH (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-06). Very rare (popmax 8.48e-05%, nfe); Associated with orthostatic hypotension 1.

What condition is associated with DBH p.Glu341= (c.1023A>G)?

DBH p.Glu341= (c.1023A>G) is associated with orthostatic hypotension 1 (ClinVar).

How common is DBH p.Glu341= (c.1023A>G) in the general population?

DBH p.Glu341= (c.1023A>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is Dopamine beta-hydroxylase deficiency inherited?

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

DBH p.Glu341=

c.1023A>G · rs374042518 · VCV1971051

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

orthostatic hypotension 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.70	donor loss · deltas
Pangolin	Δ0.58	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4.4	GERP 1.3, phastCons 1
Overall
CADD	13.28	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,076 alleles

Overall 0.000657% 1/152,230 alleles · very rare

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.Glu341=
Coding: c.1023A>G
MANE Select: NM_000787
dbSNP: rs374042518
Type: single nucleotide variant
Location: chr9:133644319 (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 341: 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 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-glu341 (accessed [today's date]).

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