Is ACADSB p.His31Arg (c.92A>G) pathogenic?

ACADSB p.His31Arg (c.92A>G) is classified Benign in ACADSB (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.0516); Low-frequency (popmax 4.68%, amr); Associated with 2-methylbutyryl-CoA dehydrogenase deficiency.

What condition is associated with ACADSB p.His31Arg (c.92A>G)?

ACADSB p.His31Arg (c.92A>G) is associated with 2-methylbutyryl-CoA dehydrogenase deficiency (ClinVar).

How common is ACADSB p.His31Arg (c.92A>G) in the general population?

ACADSB p.His31Arg (c.92A>G) is low-frequency (popmax 4.68%, amr) (gnomAD).

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.His31Arg (c.92A>G)?

AlphaMissense predicts likely benign (score 0.0516) — an in-silico prediction, not a clinical call.

ACADSB p.His31Arg

c.92A>G · rs57321698 · VCV299070

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0516 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.68%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

2-methylbutyryl-CoA dehydrogenase deficiency

Computational evidence

Protein change
AlphaMissense	0.0516	likely benign
REVEL	0.314	indeterminate
SaProt	LLR -5.34	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5	GERP -4.7
Regional constraint	o/e 1.04	unconstrained · MANE · 45 kb · p 0.39 · regional, not allelic
Overall
CADD	0.071	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 4.68% Admixed American · 2,808/60,018 alleles

Filtering AF 4.53% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.48%

Overall 0.201% 3,245/1,613,798 alleles · low-frequency

Ancestry group	Frequency	1 in
Admixed Americangrpmax	4.68%	21
East Asian	0.638%	157
Remaining individualsnot grpmax-eligible	0.122%	822
African / African-American	0.0666%	1,501
South Asian	0.0143%	7,007
European (non-Finnish)	0.00102%	98,328

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.His31Arg
Coding: c.92A>G
MANE Select: NM_001609
dbSNP: rs57321698
Type: single nucleotide variant
Location: chr10:123034405 (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 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
ACADSB p.Met389Val 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-his31arg (accessed [today's date]).

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