Is DBT p.Arg291Ter (c.871C>T) pathogenic?

DBT p.Arg291Ter (c.871C>T) is classified Pathogenic in DBT (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-03-08). Very rare (popmax 0.00267%, afr); Associated with maple syrup urine disease.

What condition is associated with DBT p.Arg291Ter (c.871C>T)?

DBT p.Arg291Ter (c.871C>T) is associated with maple syrup urine disease (ClinVar).

How common is DBT p.Arg291Ter (c.871C>T) in the general population?

DBT p.Arg291Ter (c.871C>T) is very rare (popmax 0.00267%, 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.Arg291Ter

c.871C>T · rs398123675 · VCV94015

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

maple syrup urine disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 11
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.4	GERP 1.6, phastCons 1
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,860 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000558% 9/1,613,814 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,430
Finnishnot grpmax-eligible	0.00156%	63,992
European (non-Finnish)	0.000509%	196,653

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.Arg291Ter
Coding: c.871C>T
MANE Select: NM_001918
dbSNP: rs398123675
Type: single nucleotide variant
Location: chr1:100214885 (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 291: a binding site

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.Arg291Gln Likely pathogenic ★ ⚠ same residue
DBT p.Arg291Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
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.Arg301Cys 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-arg291ter (accessed [today's date]).

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