Is BCKDHA p.Pro70= (c.210C>T) pathogenic?

BCKDHA p.Pro70= (c.210C>T) is classified Likely benign in BCKDHA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-15). Absent from gnomAD v4.1; Associated with maple syrup urine disease.

What condition is associated with BCKDHA p.Pro70= (c.210C>T)?

BCKDHA p.Pro70= (c.210C>T) is associated with maple syrup urine disease (ClinVar).

How common is BCKDHA p.Pro70= (c.210C>T) in the general population?

BCKDHA p.Pro70= (c.210C>T) 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.

BCKDHA p.Pro70=

c.210C>T · rs2513452122 · VCV2864513

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.
REVEL	0.844	moderately pathogenic-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.5	GERP 0.68, phastCons 1
Overall
CADD	11.74	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: BCKDHA
Protein: p.Pro70=
Coding: c.210C>T
MANE Select: NM_000709
dbSNP: rs2513452122
Type: single nucleotide variant
Location: chr19:41410738 (GRCh38)
Gene constraint: LOEUF 1.086 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.82 · 24 PDB
Residue 70: an α-helix

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.Pro70Ser Uncertain significance ★ ⚠ 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
BCKDHA c.376-2A>G Likely pathogenic ★★ same condition
BCKDHA c.647-1G>C 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-pro70 (accessed [today's date]).

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