Is ACADS p.Leu42= (c.126C>G) pathogenic?

ACADS p.Leu42= (c.126C>G) is classified Likely benign in ACADS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-01). Absent from gnomAD v4.1; Associated with short chain acyl-CoA dehydrogenase deficiency.

What condition is associated with ACADS p.Leu42= (c.126C>G)?

ACADS p.Leu42= (c.126C>G) is associated with short chain acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ACADS p.Leu42= (c.126C>G) in the general population?

ACADS p.Leu42= (c.126C>G) is absent from gnomAD v4.1 (gnomAD).

How is Short chain acyl-CoA dehydrogenase deficiency inherited?

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

ACADS p.Leu42=

c.126C>G · rs2501155662 · VCV2857623

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

short chain acyl-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 -5.2	GERP -3.7
Overall
CADD	0.484	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ACADS
Protein: p.Leu42=
Coding: c.126C>G
MANE Select: NM_000017
dbSNP: rs2501155662
Type: single nucleotide variant
Location: chr12:120727105 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.58 · 4 PDB
Residue 42: an α-helix

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

Disease context

short chain acyl-CoA dehydrogenase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Short chain acyl-CoA dehydrogenase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal

Similar variants

ACADS p.Leu42fs Likely pathogenic ★ same residue
ACADS c.211-2A>G Likely pathogenic ★★ same condition
ACADS c.625-1G>A Likely pathogenic ★★ same condition
ACADS c.795+1G>A Pathogenic/Likely pathogenic ★★ same condition
ACADS p.Ala199Val Likely pathogenic ★★ ⚠ same condition
ACADS p.Arg107Cys Pathogenic ★★ ⚠ same condition
ACADS p.Arg272Cys Pathogenic/Likely pathogenic ★★ same condition
ACADS p.Arg325Gln 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/acads-p-leu42 (accessed [today's date]).

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