Is BCKDHB p.Phe35fs (c.93_103dup) pathogenic?

BCKDHB p.Phe35fs (c.93103dup) is classified Pathogenic/Likely pathogenic in BCKDHB (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-07-28). Very rare (popmax 0.0023%, eas); Associated with maple syrup urine disease type 1A.

What condition is associated with BCKDHB p.Phe35fs (c.93_103dup)?

BCKDHB p.Phe35fs (c.93_103dup) is associated with maple syrup urine disease type 1A, maple syrup urine disease, maple syrup urine disease type 1B (ClinVar).

How common is BCKDHB p.Phe35fs (c.93_103dup) in the general population?

BCKDHB p.Phe35fs (c.93_103dup) is very rare (popmax 0.0023%, eas) (gnomAD).

How is Maple syrup urine disease inherited?

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

BCKDHB p.Phe35fs

c.93_103dup · rs398124601 · VCV189101

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0023%, eas)

Conditions

maple syrup urine disease type 1A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.049	GERP -3

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0023% East Asian · 1/43,386 alleles

Filtering AF 0.000362% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000262%

Overall 0.000766% 11/1,436,956 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0023%	43,386
African / African-American	0.00134%	74,432
European (non-Finnish)	0.00077%	129,894

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: BCKDHB
Protein: p.Phe35fs
Coding: c.93_103dup
MANE Select: NM_183050
dbSNP: rs398124601
Type: Microsatellite
Location: chr6:80106772 (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 type 1A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: maple syrup urine disease maple syrup urine disease type 1B

For Maple syrup urine disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

BCKDHB p.Pro366fs Pathogenic/Likely pathogenic ★★ same condition
BCKDHB p.Ser199_Pro200insTer Pathogenic ★★ same condition
BCKDHB c.1039-7_1039-4del Likely pathogenic ★ same condition
BCKDHB p.Leu194fs 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-phe35fs (accessed [today's date]).

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