Is DBT p.Arg462fs (c.1385del) pathogenic?

DBT p.Arg462fs (c.1385del) is classified Likely pathogenic in DBT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-04). Absent from gnomAD; Associated with maple syrup urine disease.

What condition is associated with DBT p.Arg462fs (c.1385del)?

DBT p.Arg462fs (c.1385del) is associated with maple syrup urine disease (ClinVar).

How common is DBT p.Arg462fs (c.1385del) in the general population?

DBT p.Arg462fs (c.1385del) is absent from gnomAD (gnomAD).

How is Maple syrup urine disease inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

DBT p.Arg462fs

c.1385del · rs2524063273 · VCV2674737

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

maple syrup urine disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (11 of 11) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.3	GERP 1.3, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DBT
Protein: p.Arg462fs
Coding: c.1385del
MANE Select: NM_001918
dbSNP: rs2524063273
Type: Deletion
Location: chr1:100196319 (GRCh38)
Gene constraint: LOEUF 1.255 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.71 · 5 PDB

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

Disease context

maple syrup urine disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Maple syrup urine disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

DBT p.Arg462Pro Pathogenic ★★ same residue
DBT p.Arg462Cys Likely pathogenic ★ ⚠ same residue
DBT p.Arg462His Uncertain significance ★ ⚠ same residue
DBT c.434-15_434-4del Pathogenic/Likely pathogenic ★★ same condition
DBT p.Cys26fs Pathogenic ★★ same condition
DBT p.Phe276fs Pathogenic/Likely pathogenic ★★ same condition
DBT p.Thr153fs Pathogenic/Likely pathogenic ★★ same condition
DBT p.Thr388_Thr389insTer Likely pathogenic ★★ 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/dbt-p-arg462fs (accessed [today's date]).

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