Is DBH p.Asp460Val (c.1379A>T) pathogenic?

DBH p.Asp460Val (c.1379A>T) is classified Uncertain significance in DBH (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-15). AlphaMissense: likely pathogenic (0.8378); Very rare (popmax 0.000848%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DBH p.Asp460Val (c.1379A>T)?

DBH p.Asp460Val (c.1379A>T) is associated with Inborn genetic diseases (ClinVar).

How common is DBH p.Asp460Val (c.1379A>T) in the general population?

DBH p.Asp460Val (c.1379A>T) is very rare (popmax 0.000848%, nfe) (gnomAD).

What do computational predictors say about DBH p.Asp460Val (c.1379A>T)?

AlphaMissense predicts likely pathogenic (score 0.8378) — an in-silico prediction, not a clinical call.

DBH p.Asp460Val

c.1379A>T · rs1260480723 · VCV2318236

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8378 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000848%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8378	likely pathogenic
REVEL	0.891	moderately pathogenic-leaning
SaProt	LLR -15.50	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.2, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 22 kb · p 0.96 · regional, not allelic
Overall
CADD	26.9	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 0.000848% European (non-Finnish) · 10/1,179,646 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.00062% 10/1,613,134 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
Protein: p.Asp460Val
Coding: c.1379A>T
MANE Select: NM_000787
dbSNP: rs1260480723
Type: single nucleotide variant
Location: chr9:133652944 (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 460: 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

Similar variants

DBH p.Asp460Gly Uncertain significance ★ ⚠ same residue
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

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-asp460val (accessed [today's date]).

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