Is DBT p.Cys26Arg (c.76T>C) pathogenic?

DBT p.Cys26Arg (c.76T>C) is classified Benign/Likely benign in DBT (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-31). AlphaMissense: likely benign (0.0679); Rare (popmax 0.898%, afr); Associated with maple syrup urine disease.

What condition is associated with DBT p.Cys26Arg (c.76T>C)?

DBT p.Cys26Arg (c.76T>C) is associated with maple syrup urine disease (ClinVar).

How common is DBT p.Cys26Arg (c.76T>C) in the general population?

DBT p.Cys26Arg (c.76T>C) is rare (popmax 0.898%, afr) (gnomAD).

How is Maple syrup urine disease inherited?

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

What do computational predictors say about DBT p.Cys26Arg (c.76T>C)?

AlphaMissense predicts likely benign (score 0.0679) — an in-silico prediction, not a clinical call.

DBT p.Cys26Arg

c.76T>C · rs145674833 · VCV94013

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0679 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.898%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

maple syrup urine disease

Computational evidence

Protein change
AlphaMissense	0.0679	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -6.17	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.74 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.1	GERP -2.9
Regional constraint	o/e 0.88	unconstrained · MANE · 54 kb · p 0.0036 · regional, not allelic
Overall
CADD	12.02	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.898% African / African-American · 674/75,036 alleles

Filtering AF 0.842% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.82%

Overall 0.0498% 804/1,613,268 alleles · rare exomes 368/1,460,926 · genomes 436/152,342 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.898%	111
Admixed American	0.137%	732
Remaining individualsnot grpmax-eligible	0.0656%	1,524
European (non-Finnish)	0.000594%	168,481

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.Cys26Arg
Coding: c.76T>C
MANE Select: NM_001918
dbSNP: rs145674833
Type: single nucleotide variant
Location: chr1:100240860 (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.Cys26fs Pathogenic ★★ 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.Arg291Ter 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-cys26arg (accessed [today's date]).

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