Is BCKDHB p.Ser76= (c.228T>A) pathogenic?

BCKDHB p.Ser76= (c.228T>A) is classified Likely benign in BCKDHB (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-29). Very rare (popmax 8.48e-05%, nfe); Associated with maple syrup urine disease.

What condition is associated with BCKDHB p.Ser76= (c.228T>A)?

BCKDHB p.Ser76= (c.228T>A) is associated with maple syrup urine disease (ClinVar).

How common is BCKDHB p.Ser76= (c.228T>A) in the general population?

BCKDHB p.Ser76= (c.228T>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is Maple syrup urine disease inherited?

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

BCKDHB p.Ser76=

c.228T>A · rs761814478 · VCV1585226

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

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 0.094	GERP -2.4
Overall
CADD	5.003	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,506 alleles

Overall 6.2e-05% 1/1,613,428 alleles · very rare exomes 1/1,461,134 · genomes 0/152,294 · joint denominator

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.Ser76=
Coding: c.228T>A
MANE Select: NM_183050
dbSNP: rs761814478
Type: single nucleotide variant
Location: chr6:80127578 (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 76: 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 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
BCKDHB c.477+1G>A 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-ser76 (accessed [today's date]).

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