Is ACADM p.Ser320fs (c.957_958del) pathogenic?

ACADM p.Ser320fs (c.957958del) is classified Pathogenic in ACADM (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-06-06). Very rare (popmax 0.000593%, nfe); Associated with medium chain acyl-CoA dehydrogenase deficiency.

What condition is associated with ACADM p.Ser320fs (c.957_958del)?

ACADM p.Ser320fs (c.957_958del) is associated with medium chain acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ACADM p.Ser320fs (c.957_958del) in the general population?

ACADM p.Ser320fs (c.957_958del) is very rare (popmax 0.000593%, nfe) (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.Ser320fs

c.957_958del · rs1057517103 · VCV371224

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

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 11 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.64	GERP -3.7, phastCons 0.006

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000593% European (non-Finnish) · 7/1,179,868 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000479% 7/1,461,626 alleles · very rare

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: ACADM
Protein: p.Ser320fs
Coding: c.957_958del
MANE Select: NM_000016
dbSNP: rs1057517103
Type: Microsatellite
Location: chr1:75761131 (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 320: 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.Ser320Ter Pathogenic/Likely pathogenic ★★ same residue
ACADM p.Ser320Leu Uncertain significance ★ ⚠ same residue
ACADM p.Ser320= Likely benign ★ same residue
ACADM p.Arg294fs Pathogenic/Likely pathogenic ★★ same condition
ACADM p.Ile135del Pathogenic/Likely pathogenic ★★ same condition
ACADM p.Arg80del Uncertain significance ★★ same condition
ACADM c.468+2_468+3delTG Likely pathogenic ★ same condition
ACADM p.Asn94fs 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/acadm-p-ser320fs (accessed [today's date]).

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