Is DBH p.Tyr327= (c.981T>C) pathogenic?

DBH p.Tyr327= (c.981T>C) is classified Likely benign in DBH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-27). Very rare (popmax 0.00401%, afr); Associated with orthostatic hypotension 1.

What condition is associated with DBH p.Tyr327= (c.981T>C)?

DBH p.Tyr327= (c.981T>C) is associated with orthostatic hypotension 1 (ClinVar).

How common is DBH p.Tyr327= (c.981T>C) in the general population?

DBH p.Tyr327= (c.981T>C) is very rare (popmax 0.00401%, 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.Tyr327=

c.981T>C · rs142042694 · VCV2084060

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00401%, 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 · T>G here scores Δ0.36 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.2	GERP -2.7
Overall
CADD	1.022	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00401% African / African-American · 3/74,892 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000248% 4/1,614,002 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,964
European (non-Finnish)	8.47e-05%	1,180,027

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.Tyr327=
Coding: c.981T>C
MANE Select: NM_000787
dbSNP: rs142042694
Type: single nucleotide variant
Location: chr9:133644277 (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 327: 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-tyr327 (accessed [today's date]).

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