Is DBT p.Arg12Gly (c.34A>G) pathogenic?

DBT p.Arg12Gly (c.34A>G) is classified Uncertain significance in DBT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-01). AlphaMissense: likely benign (0.09); Very rare (popmax 0.00668%, eas); Associated with maple syrup urine disease.

What condition is associated with DBT p.Arg12Gly (c.34A>G)?

DBT p.Arg12Gly (c.34A>G) is associated with maple syrup urine disease (ClinVar).

How common is DBT p.Arg12Gly (c.34A>G) in the general population?

DBT p.Arg12Gly (c.34A>G) is very rare (popmax 0.00668%, eas) (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.Arg12Gly (c.34A>G)?

AlphaMissense predicts likely benign (score 0.09) — an in-silico prediction, not a clinical call.

DBT p.Arg12Gly

c.34A>G · rs1215222732 · VCV1040605

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.09 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

maple syrup urine disease

Computational evidence

Protein change
AlphaMissense	0.09	likely benign
REVEL	0.076	moderately benign-leaning
SaProt	LLR -7.81	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.6	GERP -1, phastCons 0.001
Regional constraint	o/e 0.88	unconstrained · MANE · 54 kb · p 0.0036 · regional, not allelic
Overall
CADD	17.38	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% East Asian · 3/44,896 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000372% 6/1,614,110 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,965
Admixed American	0.00333%	30,006
African / African-American	0.00133%	74,940

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.Arg12Gly
Coding: c.34A>G
MANE Select: NM_001918
dbSNP: rs1215222732
Type: single nucleotide variant
Location: chr1:100249787 (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.Arg12Ser Uncertain significance ★★ ⚠ same residue
DBT p.Arg12= Likely benign ★ 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

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-arg12gly (accessed [today's date]).

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