Is ACADM p.Asp417fs (c.1250_1253delinsCT) pathogenic?

ACADM p.Asp417fs (c.12501253delinsCT) is classified Likely pathogenic in ACADM (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-16). Absent from gnomAD; Associated with medium chain acyl-CoA dehydrogenase deficiency.

What condition is associated with ACADM p.Asp417fs (c.1250_1253delinsCT)?

ACADM p.Asp417fs (c.1250_1253delinsCT) is associated with medium chain acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ACADM p.Asp417fs (c.1250_1253delinsCT) in the general population?

ACADM p.Asp417fs (c.1250_1253delinsCT) is absent from gnomAD (gnomAD).

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.Asp417fs

c.1250_1253delinsCT · rs2525706932 · VCV2679809

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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	escapes	premature termination codon in the last exon (12 of 12) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.41	GERP -2.3, phastCons 0.53

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ACADM
Protein: p.Asp417fs
Coding: c.1250_1253delinsCT
MANE Select: NM_000016
dbSNP: rs2525706932
Type: Indel
Location: chr1:75762747 (GRCh38)
Gene constraint: LOEUF 1.072 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.15 · 7 PDB
Residue 417: an α-helix

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.Asp417del Uncertain significance same residue
ACADM p.Gly265_Ala268delinsValTer Pathogenic ★★ same condition
ACADM p.Met1fs Pathogenic/Likely pathogenic ★★ same condition
ACADM p.Asp181fs 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-asp417fs (accessed [today's date]).

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