Is DBH p.Asn201Ser (c.602A>G) pathogenic?

DBH p.Asn201Ser (c.602A>G) is classified Benign in DBH (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.0594); Common (popmax 5.36%, sas) — too common for a highly-penetrant pathogenic allele; Associated with orthostatic hypotension 1.

What condition is associated with DBH p.Asn201Ser (c.602A>G)?

DBH p.Asn201Ser (c.602A>G) is associated with orthostatic hypotension 1 (ClinVar).

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.Asn201Ser (c.602A>G)?

AlphaMissense predicts likely benign (score 0.0594) — an in-silico prediction, not a clinical call.

DBH p.Asn201Ser

Q: How common is DBH p.Asn201Ser (c.602A>G) in the general population?

DBH p.Asn201Ser (c.602A>G) is common (popmax 5.36%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.602A>G · rs45465204 · VCV365640

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0594 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 5.36%, sas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

orthostatic hypotension 1

Computational evidence

Protein change
AlphaMissense	0.0594	likely benign
REVEL	0.184	benign-leaning
SaProt	LLR -5.77	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.3, phastCons 0.66
Regional constraint	o/e 1.00	unconstrained · MANE · 22 kb · p 0.96 · regional, not allelic
Overall
CADD	8.199	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.36% South Asian · 4,880/91,078 alleles

Filtering AF 5.23% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.18%

Overall 2.01% 32,459/1,614,134 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	5.36%	19
Middle Eastern	3%	33
European (non-Finnish)	2.07%	48
Remaining individualsnot grpmax-eligible	1.85%	54
Ashkenazi Jewishnot grpmax-eligible	1.81%	55
Admixed American	0.996%	100
Finnishnot grpmax-eligible	0.669%	150
African / African-American	0.267%	375
Amishnot grpmax-eligible	0.11%	912
East Asian	0.0156%	6,409

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.Asn201Ser
Coding: c.602A>G
MANE Select: NM_000787
dbSNP: rs45465204
Type: single nucleotide variant
Location: chr9:133642322 (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 201: 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-asn201ser (accessed [today's date]).

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