Is DBH p.Ala35= (c.105C>T) pathogenic?

DBH p.Ala35= (c.105C>T) is classified Benign/Likely benign in DBH (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-20). Rare (popmax 0.604%, sas); Associated with orthostatic hypotension 1.

What condition is associated with DBH p.Ala35= (c.105C>T)?

DBH p.Ala35= (c.105C>T) is associated with orthostatic hypotension 1 (ClinVar).

How common is DBH p.Ala35= (c.105C>T) in the general population?

DBH p.Ala35= (c.105C>T) is rare (popmax 0.604%, sas) (gnomAD).

How is Dopamine beta-hydroxylase deficiency inherited?

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

DBH p.Ala35=

c.105C>T · rs140025171 · VCV365630

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.604%, sas)

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 -4.8	GERP -3.4
Overall
CADD	7.913	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.604% South Asian · 550/91,078 alleles

Filtering AF 0.562% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.546%

Overall 0.0677% 1,092/1,613,070 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.604%	166
Middle Eastern	0.511%	196
Remaining individualsnot grpmax-eligible	0.08%	1,250
Admixed American	0.0533%	1,875
European (non-Finnish)	0.0353%	2,829
African / African-American	0.0107%	9,382
East Asian	0.00446%	22,427
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
Finnishnot grpmax-eligible	0.00158%	63,196

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.Ala35=
Coding: c.105C>T
MANE Select: NM_000787
dbSNP: rs140025171
Type: single nucleotide variant
Location: chr9:133636476 (GRCh38)
Gene constraint: LOEUF 0.936 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.58 · 1 PDB

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-ala35 (accessed [today's date]).

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