Is ACADSB p.Arg7fs (c.18dup) pathogenic?

ACADSB p.Arg7fs (c.18dup) is classified Likely pathogenic in ACADSB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-28). Very rare (popmax 0.000349%, nfe); Associated with 2-methylbutyryl-CoA dehydrogenase deficiency.

What condition is associated with ACADSB p.Arg7fs (c.18dup)?

ACADSB p.Arg7fs (c.18dup) is associated with 2-methylbutyryl-CoA dehydrogenase deficiency (ClinVar).

How common is ACADSB p.Arg7fs (c.18dup) in the general population?

ACADSB p.Arg7fs (c.18dup) is very rare (popmax 0.000349%, nfe) (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.Arg7fs

c.18dup · VCV3591135

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000349%, nfe)

Conditions

2-methylbutyryl-CoA dehydrogenase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.39	GERP -4

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000349% European (non-Finnish) · 4/1,146,784 alleles

Filtering AF 8.2e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.5e-05%

Overall 0.000287% 4/1,395,600 alleles · very rare

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.Arg7fs
Coding: c.18dup
MANE Select: NM_001609
Type: Duplication
Location: chr10:123009046 (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.Arg7Leu Uncertain significance ★ ⚠ same residue
ACADSB p.Glu126fs Pathogenic/Likely pathogenic ★★ same condition
ACADSB p.Val219fs Pathogenic/Likely pathogenic ★★ same condition
ACADSB c.1128+25_1128+26dup Benign/Likely benign ★★ same condition
ACADSB p.Gly293_Arg294insTer Pathogenic ★ same condition
ACADSB p.Leu23fs Likely pathogenic ★ same condition
ACADSB c.1128+2dup Uncertain significance ★ same condition
ACADSB c.1128+20_1128+26dup Likely benign ★ 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-arg7fs (accessed [today's date]).

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