Is DBT p.Ile239Val (c.715A>G) pathogenic?

DBT p.Ile239Val (c.715A>G) is classified Benign in DBT (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0554); Common (popmax 11.3%, afr) — too common for a highly-penetrant pathogenic allele; Associated with maple syrup urine disease.

What condition is associated with DBT p.Ile239Val (c.715A>G)?

DBT p.Ile239Val (c.715A>G) is associated with maple syrup urine disease (ClinVar).

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.Ile239Val (c.715A>G)?

AlphaMissense predicts likely benign (score 0.0554) — an in-silico prediction, not a clinical call.

DBT p.Ile239Val

Q: How common is DBT p.Ile239Val (c.715A>G) in the general population?

DBT p.Ile239Val (c.715A>G) is common (popmax 11.3%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.715A>G · rs72973763 · VCV94010

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0554 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 11.3%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

maple syrup urine disease

Computational evidence

Protein change
AlphaMissense	0.0554	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -4.76	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 -2	GERP -2.2
Regional constraint	o/e 0.88	unconstrained · MANE · 54 kb · p 0.0036 · regional, not allelic
Overall
CADD	0.427	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 11.3% African / African-American · 8,506/74,956 alleles

Filtering AF 11.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 11.1%

Overall 0.595% 9,596/1,613,626 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	11.3%	9
Remaining individualsnot grpmax-eligible	0.791%	126
Admixed American	0.57%	175
Middle Eastern	0.347%	288
Ashkenazi Jewishnot grpmax-eligible	0.139%	722
South Asian	0.0231%	4,337
European (non-Finnish)	0.0145%	6,899

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.Ile239Val
Coding: c.715A>G
MANE Select: NM_001918
dbSNP: rs72973763
Type: single nucleotide variant
Location: chr1:100216040 (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.Ile239Leu Uncertain significance ★ ⚠ 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-ile239val (accessed [today's date]).

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