Is DBT p.Tyr114= (c.342T>C) pathogenic?

DBT p.Tyr114= (c.342T>C) is classified Likely benign in DBT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-21). Very rare (popmax 0.00133%, afr); Associated with maple syrup urine disease.

What condition is associated with DBT p.Tyr114= (c.342T>C)?

DBT p.Tyr114= (c.342T>C) is associated with maple syrup urine disease (ClinVar).

How common is DBT p.Tyr114= (c.342T>C) in the general population?

DBT p.Tyr114= (c.342T>C) is very rare (popmax 0.00133%, afr) (gnomAD).

How is Maple syrup urine disease inherited?

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

DBT p.Tyr114=

c.342T>C · rs1207748719 · VCV727909

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

maple syrup urine disease

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 -0.68	GERP -4.2
Overall
CADD	4.572	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,930 alleles

Overall 0.000275% 4/1,455,426 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00161%	62,262
African / African-Americangrpmax	0.00133%	74,930
South Asian	0.0011%	90,934
European (non-Finnish)	8.51e-05%	1,174,417

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DBT
Protein: p.Tyr114=
Coding: c.342T>C
MANE Select: NM_001918
dbSNP: rs1207748719
Type: single nucleotide variant
Location: chr1:100230824 (GRCh38)
Gene constraint: LOEUF 1.255 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.71 · 5 PDB
Residue 114: the lipoyl-binding domain

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 c.1018-550A>G Pathogenic/Likely pathogenic ★★ same condition
DBT c.1281+1G>A Pathogenic/Likely pathogenic ★★ same condition
DBT c.1281+1G>T Pathogenic/Likely pathogenic ★★ same condition
DBT c.51+1G>T Pathogenic/Likely pathogenic ★★ same condition
DBT c.52-1G>A Pathogenic/Likely pathogenic ★★ same condition
DBT p.Arg291Ter Pathogenic ★★ same condition
DBT p.Arg301Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
DBT p.Arg376Cys Pathogenic/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-tyr114 (accessed [today's date]).

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