Is DBH p.Gln595Arg (c.1784A>G) pathogenic?

DBH p.Gln595Arg (c.1784A>G) is classified Likely benign in DBH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-26). AlphaMissense: likely benign (0.0537); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DBH p.Gln595Arg (c.1784A>G)?

DBH p.Gln595Arg (c.1784A>G) is associated with Inborn genetic diseases (ClinVar).

How common is DBH p.Gln595Arg (c.1784A>G) in the general population?

DBH p.Gln595Arg (c.1784A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DBH p.Gln595Arg (c.1784A>G)?

AlphaMissense predicts likely benign (score 0.0537) — an in-silico prediction, not a clinical call.

DBH p.Gln595Arg

c.1784A>G · VCV4616949

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0537 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0537	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -5.98	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 -1.6	GERP -2.3
Regional constraint	o/e 1.00	unconstrained · MANE · 22 kb · p 0.96 · regional, not allelic
Overall
CADD	0.005	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DBH
Protein: p.Gln595Arg
Coding: c.1784A>G
MANE Select: NM_000787
Type: single nucleotide variant
Location: chr9:133658377 (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 595: a disulfide bond; the 'disordered' region

Full DBH gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DBH p.Ala113Ser Uncertain significance ★★ ⚠ same condition
DBH p.Ala383Val Uncertain significance ★★ ⚠ same condition
DBH p.Arg43His Uncertain significance ★★ ⚠ same condition
DBH p.Arg473Gln Uncertain significance ★★ ⚠ same condition
DBH p.Arg549Leu Uncertain significance ★★ ⚠ same condition
DBH p.Arg572His Uncertain significance ★★ ⚠ same condition
DBH p.Arg6His Uncertain significance ★★ ⚠ same condition
DBH p.Arg92Cys 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-gln595arg (accessed [today's date]).

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