Is ACADS p.Leu77fs (c.226_229dup) pathogenic?

ACADS p.Leu77fs (c.226229dup) is classified Pathogenic in ACADS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-01). Associated with short chain acyl-CoA dehydrogenase deficiency.

What condition is associated with ACADS p.Leu77fs (c.226_229dup)?

ACADS p.Leu77fs (c.226_229dup) is associated with short chain acyl-CoA dehydrogenase deficiency (ClinVar).

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.Leu77fs

c.226_229dup · VCV4704035

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

short chain acyl-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 3 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1

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

Variant & gene context

Gene: ACADS
Protein: p.Leu77fs
Coding: c.226_229dup
MANE Select: NM_000017
Type: Microsatellite
Location: chr12:120736996 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.58 · 4 PDB
Residue 77: 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.Glu104del Pathogenic ★★ same condition
ACADS p.Tyr123fs Pathogenic/Likely pathogenic ★★ same condition
ACADS p.Val291fs Likely pathogenic ★ same condition
ACADS p.Asn120del Uncertain significance ★ same condition
ACADS p.Lys339del Uncertain significance ★ same condition
ACADS p.Lys73del Uncertain significance ★ same condition
ACADS c.211-2A>G Likely pathogenic ★★ same condition
ACADS c.625-1G>A 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-leu77fs (accessed [today's date]).

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