Is DBH p.Gly320Arg (c.958G>A) pathogenic?

DBH p.Gly320Arg (c.958G>A) is classified Uncertain significance in DBH (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-06-29). AlphaMissense: likely pathogenic (0.9137); Very rare (popmax 0.00534%, afr); Associated with Inborn genetic diseases.

What condition is associated with DBH p.Gly320Arg (c.958G>A)?

DBH p.Gly320Arg (c.958G>A) is associated with Inborn genetic diseases, orthostatic hypotension 1 (ClinVar).

How common is DBH p.Gly320Arg (c.958G>A) in the general population?

DBH p.Gly320Arg (c.958G>A) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about DBH p.Gly320Arg (c.958G>A)?

AlphaMissense predicts likely pathogenic (score 0.9137) — an in-silico prediction, not a clinical call.

DBH p.Gly320Arg

c.958G>A · rs896285959 · VCV840925

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9137 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9137	likely pathogenic
REVEL	0.733	pathogenic-leaning
SaProt	LLR -13.18	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.20	acceptor loss, 36 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 9.6	GERP 1.3, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 22 kb · p 0.96 · regional, not allelic
Overall
CADD	26.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00534% African / African-American · 4/74,900 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00118% 19/1,613,984 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,725
South Asian	0.00329%	30,362
Admixed American	0.00167%	60,006
Remaining individualsnot grpmax-eligible	0.0016%	62,490
European (non-Finnish)	0.000847%	117,998

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.Gly320Arg
Coding: c.958G>A
MANE Select: NM_000787
dbSNP: rs896285959
Type: single nucleotide variant
Location: chr9:133644254 (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 320: a disulfide bond

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

Also linked: orthostatic hypotension 1

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-gly320arg (accessed [today's date]).

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