Is BCKDHA p.Pro39= (c.117C>G) pathogenic?

BCKDHA p.Pro39= (c.117C>G) is classified Likely benign in BCKDHA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-19). Very rare (popmax 0.00167%, amr); Associated with maple syrup urine disease.

What condition is associated with BCKDHA p.Pro39= (c.117C>G)?

BCKDHA p.Pro39= (c.117C>G) is associated with maple syrup urine disease (ClinVar).

How common is BCKDHA p.Pro39= (c.117C>G) in the general population?

BCKDHA p.Pro39= (c.117C>G) is very rare (popmax 0.00167%, amr) (gnomAD).

How is Maple syrup urine disease inherited?

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

BCKDHA p.Pro39=

c.117C>G · rs80014754 · VCV1080941

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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 1.1	GERP 0.66, phastCons 0.095
Overall
CADD	6.94	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,018 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000248% 4/1,614,152 alleles · very rare exomes 4/1,461,862 · genomes 0/152,290 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,018
South Asian	0.0011%	91,078
European (non-Finnish)	0.000169%	590,016

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: BCKDHA
Protein: p.Pro39=
Coding: c.117C>G
MANE Select: NM_000709
dbSNP: rs80014754
Type: single nucleotide variant
Location: chr19:41410645 (GRCh38)
Gene constraint: LOEUF 1.086 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.82 · 24 PDB
Residue 39: the 'disordered' region; a UniProt-annotated variant site (in)

Full BCKDHA 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

BCKDHA p.Pro39His Benign/Likely benign ★★ same residue
BCKDHA p.Pro39Arg Likely benign ★ same residue
BCKDHA p.Pro39Ser Likely benign ★ same residue
BCKDHA c.109-1G>A Pathogenic/Likely pathogenic ★★ same condition
BCKDHA c.1168-1G>A Likely pathogenic ★★ same condition
BCKDHA c.1168-2A>G Pathogenic/Likely pathogenic ★★ same condition
BCKDHA c.288+1G>A Pathogenic ★★ same condition
BCKDHA c.288+9C>T 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/bckdha-p-pro39 (accessed [today's date]).

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