Is ACADSB p.Arg13Lys (c.38G>A) pathogenic?

ACADSB p.Arg13Lys (c.38G>A) is classified Benign in ACADSB (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.1025); Common (popmax 39.6%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with 2-methylbutyryl-CoA dehydrogenase deficiency.

What condition is associated with ACADSB p.Arg13Lys (c.38G>A)?

ACADSB p.Arg13Lys (c.38G>A) is associated with 2-methylbutyryl-CoA dehydrogenase deficiency (ClinVar).

How is 2-methylbutyryl-CoA dehydrogenase deficiency inherited?

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

What do computational predictors say about ACADSB p.Arg13Lys (c.38G>A)?

AlphaMissense predicts likely benign (score 0.1025) — an in-silico prediction, not a clinical call.

ACADSB p.Arg13Lys

Q: How common is ACADSB p.Arg13Lys (c.38G>A) in the general population?

ACADSB p.Arg13Lys (c.38G>A) is common (popmax 39.6%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.38G>A · rs12263012 · VCV299068

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.1025 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 39.6%, nfe) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

2-methylbutyryl-CoA dehydrogenase deficiency

Computational evidence

Protein change
AlphaMissense	0.1025	likely benign
REVEL	0.165	moderately benign-leaning
SaProt	LLR -7.27	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -1.8, phastCons 0.28
Regional constraint	o/e 1.04	unconstrained · MANE · 45 kb · p 0.39 · regional, not allelic
Overall
CADD	15.94	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 39.6% European (non-Finnish) · 453,657/1,146,568 alleles

Filtering AF 39.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 39.4%

Overall 36.2% 559,209/1,546,378 alleles · common

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	44.3%	2
European (non-Finnish)grpmax	39.6%	3
Amishnot grpmax-eligible	35.9%	3
Ashkenazi Jewishnot grpmax-eligible	34.9%	3
Remaining individualsnot grpmax-eligible	33.9%	3
Admixed American	27.1%	4
Middle Eastern	26.6%	4
South Asian	25.2%	4
East Asian	12.1%	8
African / African-American	12%	8

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg13Lys
Coding: c.38G>A
MANE Select: NM_001609
dbSNP: rs12263012
Type: single nucleotide variant
Location: chr10:123009067 (GRCh38)
Gene constraint: LOEUF 0.891 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.47 · 1 PDB
Residue 13: a UniProt-annotated variant site (in)

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.Arg13Ser 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-arg13lys (accessed [today's date]).

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