Is BCKDHB p.Pro89= (c.267T>G) pathogenic?

BCKDHB p.Pro89= (c.267T>G) is classified Likely benign in BCKDHB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-02). Absent from gnomAD v4.1; Associated with maple syrup urine disease.

What condition is associated with BCKDHB p.Pro89= (c.267T>G)?

BCKDHB p.Pro89= (c.267T>G) is associated with maple syrup urine disease (ClinVar).

How common is BCKDHB p.Pro89= (c.267T>G) in the general population?

BCKDHB p.Pro89= (c.267T>G) is absent from gnomAD v4.1 (gnomAD).

How is Maple syrup urine disease inherited?

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

BCKDHB p.Pro89=

c.267T>G · rs1582191955 · VCV2843844

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

maple syrup urine disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.13	GERP -0.99, phastCons 0.98
Overall
CADD	7.588	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BCKDHB
Protein: p.Pro89=
Coding: c.267T>G
MANE Select: NM_183050
dbSNP: rs1582191955
Type: single nucleotide variant
Location: chr6:80127617 (GRCh38)
Gene constraint: LOEUF 1.206 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.86 · 24 PDB

Full BCKDHB 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

BCKDHB p.Pro89Leu Uncertain significance ★ ⚠ same residue
BCKDHB c.1038+2T>C Likely pathogenic ★★ same condition
BCKDHB c.1039-2A>G Pathogenic/Likely pathogenic ★★ same condition
BCKDHB c.196+1G>A Likely pathogenic ★★ same condition
BCKDHB c.274+1G>T Pathogenic/Likely pathogenic ★★ same condition
BCKDHB c.274+2T>C Likely pathogenic ★★ same condition
BCKDHB c.275-2A>G Pathogenic ★★ same condition
BCKDHB c.343+2T>G 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/bckdhb-p-pro89 (accessed [today's date]).

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