Is DBH p.Glu204Lys (c.610G>A) pathogenic?

DBH p.Glu204Lys (c.610G>A) is classified Uncertain significance in DBH (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-06). AlphaMissense: likely benign (0.0706); Ultra-rare (popmax 0.0183%, amr); Associated with orthostatic hypotension 1.

What condition is associated with DBH p.Glu204Lys (c.610G>A)?

DBH p.Glu204Lys (c.610G>A) is associated with orthostatic hypotension 1 (ClinVar).

How common is DBH p.Glu204Lys (c.610G>A) in the general population?

DBH p.Glu204Lys (c.610G>A) is ultra-rare (popmax 0.0183%, amr) (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.Glu204Lys (c.610G>A)?

AlphaMissense predicts likely benign (score 0.0706) — an in-silico prediction, not a clinical call.

DBH p.Glu204Lys

c.610G>A · rs373889996 · VCV1987711

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0706 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0183%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

orthostatic hypotension 1

Computational evidence

Protein change
AlphaMissense	0.0706	likely benign
REVEL	0.099	moderately benign-leaning
SaProt	LLR -7.08	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 -3.8	GERP -2.7
Regional constraint	o/e 1.00	unconstrained · MANE · 22 kb · p 0.96 · regional, not allelic
Overall
CADD	0.003	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.0183% Admixed American · 11/60,016 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00785%

Overall 0.0039% 63/1,614,140 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0183%	5,456
African / African-American	0.00666%	15,007
European (non-Finnish)	0.00373%	26,819
Remaining individualsnot grpmax-eligible	0.0032%	31,255
East Asian	0.00223%	44,866

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.Glu204Lys
Coding: c.610G>A
MANE Select: NM_000787
dbSNP: rs373889996
Type: single nucleotide variant
Location: chr9:133642330 (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 204: a disulfide bond; an α-helix

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-glu204lys (accessed [today's date]).

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