Is BCKDHB p.Pro366fs (c.1095_1096del) pathogenic?

BCKDHB p.Pro366fs (c.10951096del) is classified Pathogenic/Likely pathogenic in BCKDHB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-29). No gnomAD frequency available for this variant; Associated with maple syrup urine disease.

What condition is associated with BCKDHB p.Pro366fs (c.1095_1096del)?

BCKDHB p.Pro366fs (c.1095_1096del) is associated with maple syrup urine disease (ClinVar).

How common is BCKDHB p.Pro366fs (c.1095_1096del) in the general population?

BCKDHB p.Pro366fs (c.1095_1096del) is no gnomAD frequency available for this variant (gnomAD).

How is Maple syrup urine disease inherited?

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

BCKDHB p.Pro366fs

c.1095_1096del · rs2483370839 · VCV2680135

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

maple syrup urine disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (10 of 10) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BCKDHB
Protein: p.Pro366fs
Coding: c.1095_1096del
MANE Select: NM_183050
dbSNP: rs2483370839
Type: Microsatellite
Location: chr6:80343716 (GRCh38)
Gene constraint: LOEUF 1.206 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.86 · 24 PDB
Residue 366: an α-helix

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.Pro366Leu Uncertain significance ★ ⚠ same residue
BCKDHB p.Phe35fs Pathogenic/Likely pathogenic ★★ same condition
BCKDHB p.Ser199_Pro200insTer Pathogenic ★★ same condition
BCKDHB c.1039-7_1039-4del Likely pathogenic ★ same condition
BCKDHB p.Trp10fs Pathogenic ★ same condition
BCKDHB c.1039-10_1039-9del Uncertain significance ★ same condition
BCKDHB c.478-13_478-10del Likely benign ★ same condition
BCKDHB c.1038+2T>C 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-pro366fs (accessed [today's date]).

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