Is DBT c.1209+9T>C pathogenic?

DBT c.1209+9T>C is classified Likely benign in DBT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-08). Very rare (popmax 0.0066%, sas); Associated with maple syrup urine disease.

What condition is associated with DBT c.1209+9T>C?

DBT c.1209+9T>C is associated with maple syrup urine disease (ClinVar).

How common is DBT c.1209+9T>C in the general population?

DBT c.1209+9T>C is very rare (popmax 0.0066%, sas) (gnomAD).

How is Maple syrup urine disease inherited?

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

DBT c.1209+9T>C

rs772021583 · VCV2853645

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0066%, sas)

Conditions

maple syrup urine disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +9	near-intronic (+9 nt from the splice site)
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.32 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.16	GERP -3.9
Overall
CADD	5.717	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0066% South Asian · 6/90,906 alleles

Filtering AF 0.00287% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.000413% 6/1,451,994 alleles · very rare

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.1209+9T>C
MANE Select: NM_001918
dbSNP: rs772021583
Type: single nucleotide variant
Location: chr1:100206436 (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-c-1209-plus-9t-c (accessed [today's date]).

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