Is DBH p.Leu552= (c.1656G>A) pathogenic?

DBH p.Leu552= (c.1656G>A) is classified Likely benign in DBH (ClinVar, Single submitter, 1 submitter; last evaluated 2018-09-10). Absent from gnomAD v4.1.

How common is DBH p.Leu552= (c.1656G>A) in the general population?

DBH p.Leu552= (c.1656G>A) is absent from gnomAD v4.1 (gnomAD).

DBH p.Leu552=

c.1656G>A · rs777841494 · VCV750958

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.24	GERP -3
Overall
CADD	3.653	PHRED · no single calibrated threshold — expert panels disagree

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.Leu552=
Coding: c.1656G>A
MANE Select: NM_000787
dbSNP: rs777841494
Type: single nucleotide variant
Location: chr9:133657163 (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 552: a disulfide bond; an α-helix

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

Similar variants

DBH c.339+2T>C Pathogenic ★★ same type
DBH c.1024+6C>T Uncertain significance ★★ same type
DBH c.486+15C>T Uncertain significance ★★ same type
DBH c.*393C>T Uncertain significance ★★ same type
DBH p.Ala113Ser Uncertain significance ★★ ⚠ same type
DBH p.Ala259Val Uncertain significance ★★ ⚠ same type
DBH p.Ala383Val Uncertain significance ★★ ⚠ same type
DBH p.Ala506Thr Uncertain significance ★★ ⚠ same type

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-leu552 (accessed [today's date]).

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