Is DBT c.175+37G>A pathogenic?

DBT c.175+37G>A is classified Benign/Likely benign in DBT (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-04-11). Low-frequency (popmax 1.81%, eas); Associated with maple syrup urine disease.

What condition is associated with DBT c.175+37G>A?

DBT c.175+37G>A is associated with maple syrup urine disease (ClinVar).

How common is DBT c.175+37G>A in the general population?

DBT c.175+37G>A is low-frequency (popmax 1.81%, eas) (gnomAD).

How is Maple syrup urine disease inherited?

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

DBT c.175+37G>A

rs76902654 · VCV93996

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.81%, eas)

Conditions

maple syrup urine disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type.
Splicing
Splice region	donor +37	near-intronic (+37 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Non-coding constraint	Z 1.07	1 kb window · o/e 0.92 · regional · uncalibrated
Overall
CADD	7.918	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.81% East Asian · 803/44,274 alleles

Filtering AF 1.71% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.67%

Overall 0.14% 2,150/1,532,784 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.81%	55
Finnishnot grpmax-eligible	0.592%	169
Remaining individualsnot grpmax-eligible	0.342%	292
South Asian	0.224%	446
Middle Eastern	0.115%	866
African / African-American	0.0888%	1,127
European (non-Finnish)	0.043%	2,325
Ashkenazi Jewishnot grpmax-eligible	0.0241%	4,154
Admixed American	0.0201%	4,981

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
Coding: c.175+37G>A
MANE Select: NM_001918
dbSNP: rs76902654
Type: single nucleotide variant
Location: chr1:100240724 (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

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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-c-175-plus-37g-a (accessed [today's date]).

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