Is DBT p.Asp251= (c.753C>T) pathogenic?

DBT p.Asp251= (c.753C>T) is classified Conflicting classifications of pathogenicity in DBT (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-02-01). Rare (popmax 0.281%, nfe); Associated with maple syrup urine disease.

What condition is associated with DBT p.Asp251= (c.753C>T)?

DBT p.Asp251= (c.753C>T) is associated with maple syrup urine disease (ClinVar).

How common is DBT p.Asp251= (c.753C>T) in the general population?

DBT p.Asp251= (c.753C>T) is rare (popmax 0.281%, nfe) (gnomAD).

How is Maple syrup urine disease inherited?

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

DBT p.Asp251=

c.753C>T · rs79292123 · VCV94012

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.281%, nfe)

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 1.9	GERP 0.95, phastCons 1
Overall
CADD	8.492	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.281% European (non-Finnish) · 3,279/1,165,272 alleles

Filtering AF 0.273% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.27%

Overall 0.228% 3,644/1,597,734 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.281%	355
Remaining individualsnot grpmax-eligible	0.182%	549
Admixed American	0.17%	588
South Asian	0.12%	833
Amishnot grpmax-eligible	0.11%	912
African / African-American	0.0496%	2,016
Finnishnot grpmax-eligible	0.00313%	31,993
East Asian	0.00223%	44,774

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.Asp251=
Coding: c.753C>T
MANE Select: NM_001918
dbSNP: rs79292123
Type: single nucleotide variant
Location: chr1:100216002 (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 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-asp251 (accessed [today's date]).

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