Is DBT p.Ala2fs (c.4del) pathogenic?

DBT p.Ala2fs (c.4del) is classified Likely pathogenic in DBT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-10). Associated with maple syrup urine disease type 2.

What condition is associated with DBT p.Ala2fs (c.4del)?

DBT p.Ala2fs (c.4del) is associated with maple syrup urine disease type 2 (ClinVar).

How is Maple syrup urine disease inherited?

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

DBT p.Ala2fs

c.4del · VCV3583658

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

maple syrup urine disease type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.6	GERP 1.9, phastCons 1

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

Variant & gene context

Gene: DBT
Protein: p.Ala2fs
Coding: c.4del
MANE Select: NM_001918
Type: Deletion
Location: chr1:100249817 (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 type 2 — 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.Cys26fs Pathogenic ★★ same condition
DBT p.Lys120fs Pathogenic ★★ same condition
DBT p.Pro238fs Pathogenic ★★ same condition
DBT p.Ala2Thr Uncertain significance ★★ ⚠ same residue
DBT c.434-3125_434-10del Pathogenic ★ same condition
DBT p.Ala300fs Pathogenic ★ same condition
DBT p.Phe53_Leu54insTer Likely pathogenic ★ same condition
DBT p.Ala2Val Conflicting classifications of pathogenicity ★ ⚠ same residue

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-ala2fs (accessed [today's date]).

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