Is DBT p.Cys26fs (c.75_76del) pathogenic?

DBT p.Cys26fs (c.7576del) is classified Pathogenic in DBT (ClinVar, Multiple submitters, 15 submitters; last evaluated 2026-07-18). Very rare (popmax 0.0067%, eas); Associated with DBT-related disorder.

What condition is associated with DBT p.Cys26fs (c.75_76del)?

DBT p.Cys26fs (c.75_76del) is associated with DBT-related disorder, maple syrup urine disease, maple syrup urine disease type 1A (ClinVar).

How common is DBT p.Cys26fs (c.75_76del) in the general population?

DBT p.Cys26fs (c.75_76del) is very rare (popmax 0.0067%, eas) (gnomAD).

DBT p.Cys26fs

c.75_76del · rs768832921 · VCV11950

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 15 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0067%, eas)

Conditions

DBT-related disorder

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 2 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.21	GERP 0.57
Overall
CADD	22.3	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 0.0067% East Asian · 3/44,798 alleles

Filtering AF 0.00386% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00353%

Overall 0.00508% 82/1,613,208 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0507%	1,973
East Asiangrpmax	0.0067%	14,933
European (non-Finnish)	0.00492%	20,335
Admixed American	0.00333%	29,994
Remaining individualsnot grpmax-eligible	0.0032%	31,231
African / African-American	0.00134%	74,898
South Asian	0.0011%	91,040

Ashkenazi Jewish 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.Cys26fs
Coding: c.75_76del
MANE Select: NM_001918
dbSNP: rs768832921
Type: Deletion
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

DBT-related disorder

Also linked: maple syrup urine disease maple syrup urine disease type 1A maple syrup urine disease type 2

Similar variants

DBT p.Cys26Arg Benign/Likely benign ★★ same residue
DBT c.434-15_434-4del Pathogenic/Likely pathogenic ★★ same condition
DBT p.Lys120fs Pathogenic ★★ same condition
DBT p.Phe276fs Pathogenic/Likely pathogenic ★★ same condition
DBT p.Pro238fs Pathogenic ★★ same condition
DBT p.Thr153fs Pathogenic/Likely pathogenic ★★ same condition
DBT p.Thr388_Thr389insTer Likely pathogenic ★★ same condition
DBT p.Thr91fs 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-cys26fs (accessed [today's date]).

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