Is ACADSB p.Pro242= (c.726G>A) pathogenic?

ACADSB p.Pro242= (c.726G>A) is classified Benign in ACADSB (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-03). Rare (popmax 0.222%, amr); Associated with 2-methylbutyryl-CoA dehydrogenase deficiency.

What condition is associated with ACADSB p.Pro242= (c.726G>A)?

ACADSB p.Pro242= (c.726G>A) is associated with 2-methylbutyryl-CoA dehydrogenase deficiency (ClinVar).

How common is ACADSB p.Pro242= (c.726G>A) in the general population?

ACADSB p.Pro242= (c.726G>A) is rare (popmax 0.222%, amr) (gnomAD).

How is 2-methylbutyryl-CoA dehydrogenase deficiency inherited?

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

ACADSB p.Pro242=

c.726G>A · rs148114788 · VCV703330

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.222%, amr)

Conditions

2-methylbutyryl-CoA dehydrogenase deficiency

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 0.59	GERP -2.4, phastCons 0.94
Overall
CADD	6.181	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.222% Admixed American · 133/60,002 alleles

Filtering AF 0.191% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.179%

Overall 0.0147% 238/1,613,720 alleles · rare exomes 224/1,461,544 · genomes 14/152,176 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.222%	451
European (non-Finnish)	0.00822%	12,162
East Asian	0.00669%	14,955
Remaining individualsnot grpmax-eligible	0.0048%	20,831
African / African-American	0.00267%	37,491

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: ACADSB
Protein: p.Pro242=
Coding: c.726G>A
MANE Select: NM_001609
dbSNP: rs148114788
Type: single nucleotide variant
Location: chr10:123043090 (GRCh38)
Gene constraint: LOEUF 0.891 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.47 · 1 PDB

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

Disease context

2-methylbutyryl-CoA dehydrogenase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For 2-methylbutyryl-CoA dehydrogenase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ACADSB p.Pro242Leu Uncertain significance ★ ⚠ same residue
ACADSB c.1128+1G>A Likely pathogenic ★★ same condition
ACADSB c.1228+1G>A Likely pathogenic ★★ same condition
ACADSB c.303+3A>G Pathogenic/Likely pathogenic ★★ same condition
ACADSB p.Cys308Tyr Pathogenic/Likely pathogenic ★★ same condition
ACADSB p.Gln99Ter Pathogenic/Likely pathogenic ★★ same condition
ACADSB p.Glu387Lys Pathogenic/Likely pathogenic ★★ same condition
ACADSB p.Gly410Ser 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/acadsb-p-pro242 (accessed [today's date]).

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