Is ACADSB p.Ala367Val (c.1100C>T) pathogenic?

ACADSB p.Ala367Val (c.1100C>T) is classified Uncertain significance in ACADSB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-12). AlphaMissense: ambiguous (0.4196); Very rare (popmax 0.00447%, amr); Associated with 2-methylbutyryl-CoA dehydrogenase deficiency.

What condition is associated with ACADSB p.Ala367Val (c.1100C>T)?

ACADSB p.Ala367Val (c.1100C>T) is associated with 2-methylbutyryl-CoA dehydrogenase deficiency (ClinVar).

How common is ACADSB p.Ala367Val (c.1100C>T) in the general population?

ACADSB p.Ala367Val (c.1100C>T) is very rare (popmax 0.00447%, 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.Ala367Val (c.1100C>T)?

AlphaMissense predicts ambiguous (score 0.4196) — an in-silico prediction, not a clinical call.

ACADSB p.Ala367Val

c.1100C>T · rs745900584 · VCV1434993

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4196 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00447%, amr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

2-methylbutyryl-CoA dehydrogenase deficiency

Computational evidence

Protein change
AlphaMissense	0.4196	ambiguous
REVEL	0.929	moderately pathogenic-leaning
SaProt	LLR -10.22	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 45 kb · p 0.39 · regional, not allelic
Overall
CADD	29.8	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 0.00447% Admixed American · 2/44,758 alleles

Filtering AF 0.000741% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000784% 11/1,403,428 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00447%	22,379
Remaining individualsnot grpmax-eligible	0.0038%	26,322
East Asian	0.00298%	33,516
South Asian	0.00254%	39,350
European (non-Finnish)	0.000377%	265,038

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.Ala367Val
Coding: c.1100C>T
MANE Select: NM_001609
dbSNP: rs745900584
Type: single nucleotide variant
Location: chr10:123051158 (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 367: an α-helix

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.Ala367= Likely benign ★★ 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-ala367val (accessed [today's date]).

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