Is BCKDHA p.Pro38= (c.114C>G) pathogenic?

BCKDHA p.Pro38= (c.114C>G) is classified Benign/Likely benign in BCKDHA (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-01). Low-frequency (popmax 1.82%, afr); Associated with Inborn genetic diseases.

What condition is associated with BCKDHA p.Pro38= (c.114C>G)?

BCKDHA p.Pro38= (c.114C>G) is associated with Inborn genetic diseases, maple syrup urine disease, maple syrup urine disease type 1A (ClinVar).

How common is BCKDHA p.Pro38= (c.114C>G) in the general population?

BCKDHA p.Pro38= (c.114C>G) is low-frequency (popmax 1.82%, afr) (gnomAD).

BCKDHA p.Pro38=

c.114C>G · rs11549935 · VCV93337

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.82%, afr)

Conditions

Inborn genetic diseases

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 -1.8	GERP -3.4
Overall
CADD	0.787	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.82% African / African-American · 1,364/75,008 alleles

Filtering AF 1.74% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.71%

Overall 0.0968% 1,563/1,614,136 alleles · low-frequency exomes 781/1,461,872 · genomes 782/152,264 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.82%	55
Remaining individualsnot grpmax-eligible	0.146%	687
Admixed American	0.118%	845
Middle Eastern	0.0165%	6,060
South Asian	0.0121%	8,280
European (non-Finnish)	0.00212%	47,201

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.Pro38=
Coding: c.114C>G
MANE Select: NM_000709
dbSNP: rs11549935
Type: single nucleotide variant
Location: chr19:41410642 (GRCh38)
Gene constraint: LOEUF 1.086 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.82 · 24 PDB
Residue 38: the 'disordered' region

Full BCKDHA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

BCKDHA p.Pro38Ser 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-pro38 (accessed [today's date]).

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