Is DBH c.744+4del pathogenic?

DBH c.744+4del is classified Uncertain significance in DBH (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-22). Very rare (popmax 0.00171%, amr); Associated with Inborn genetic diseases.

What condition is associated with DBH c.744+4del?

DBH c.744+4del is associated with Inborn genetic diseases, orthostatic hypotension 1 (ClinVar).

How common is DBH c.744+4del in the general population?

DBH c.744+4del is very rare (popmax 0.00171%, amr) (gnomAD).

DBH c.744+4del

rs1832129067 · VCV1401102

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00171%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +4	donor splice region (+4, within the first 6 intronic nt) · inside the BP7-excluded zone
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.4	GERP -0.62, phastCons 0.99
Non-coding constraint	Z 3.28	1 kb window · o/e 0.75 · regional · uncalibrated
Overall
CADD	0.001	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00171% Admixed American · 1/58,606 alleles

Overall 0.000657% 1/152,218 alleles · very rare

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
Coding: c.744+4del
MANE Select: NM_000787
dbSNP: rs1832129067
Type: Deletion
Location: chr9:133642468 (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

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

Also linked: orthostatic hypotension 1

Similar variants

DBH p.Leu500fs Pathogenic/Likely pathogenic ★★ same condition
DBH p.Gly316fs Pathogenic ★ same condition
DBH c.1191+6_1191+9del Uncertain significance ★ same condition
DBH c.745-14_745-13del Uncertain significance ★ same condition
DBH p.His564fs Uncertain significance ★ same condition
DBH p.Leu386del Uncertain significance ★ same condition
DBH c.1374+16del Benign ★ same condition
DBH c.1562+16_1562+28del Likely benign ★ 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-c-744-plus-4del (accessed [today's date]).

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