Is ACADM p.Asp181fs (c.541_552delinsATATC) pathogenic?

ACADM p.Asp181fs (c.541552delinsATATC) is classified Pathogenic in ACADM (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-01). Associated with medium chain acyl-CoA dehydrogenase deficiency.

What condition is associated with ACADM p.Asp181fs (c.541_552delinsATATC)?

ACADM p.Asp181fs (c.541_552delinsATATC) is associated with medium chain acyl-CoA dehydrogenase deficiency (ClinVar).

How is Medium chain acyl-CoA dehydrogenase deficiency inherited?

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

ACADM p.Asp181fs

c.541_552delinsATATC · VCV3385404

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

medium 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 7 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.8	GERP 1, phastCons 1

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

Variant & gene context

Gene: ACADM
Protein: p.Asp181fs
Coding: c.541_552delinsATATC
MANE Select: NM_000016
Type: Indel
Location: chr1:75740052 (GRCh38)
Gene constraint: LOEUF 1.072 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.15 · 7 PDB

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

Disease context

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

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

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

ACADM p.Asp181Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
ACADM p.Gly265_Ala268delinsValTer Pathogenic ★★ same condition
ACADM p.Met1fs Pathogenic/Likely pathogenic ★★ same condition
ACADM p.Asp417fs Likely pathogenic ★ same condition
ACADM p.Gly275fs Likely pathogenic ★ same condition
ACADM p.Ser346fs Likely pathogenic ★ same condition
ACADM p.Arg294Ile Uncertain significance ★ same condition
ACADM p.Gly118Arg Uncertain significance ★ 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/acadm-p-asp181fs (accessed [today's date]).

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