Is ACADM p.Trp82fs (c.244dup) pathogenic?

ACADM p.Trp82fs (c.244dup) is classified Pathogenic in ACADM (ClinVar, Multiple submitters, 16 submitters; last evaluated 2026-04-29). Very rare (popmax 0.00186%, nfe); Associated with MCADD - Medium-chain acyl-CoA dehydrogenase deficiency – full ACADM sequencing newborn screening follow up.

How common is ACADM p.Trp82fs (c.244dup) in the general population?

ACADM p.Trp82fs (c.244dup) is very rare (popmax 0.00186%, nfe) (gnomAD).

ACADM p.Trp82fs

Q: What condition is associated with ACADM p.Trp82fs (c.244dup)?

ACADM p.Trp82fs (c.244dup) is associated with MCADD - Medium-chain acyl-CoA dehydrogenase deficiency – full ACADM sequencing newborn screening follow up, medium chain acyl-CoA dehydrogenase deficiency (ClinVar).

c.244dup · rs786204566 · VCV188934

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 16 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00186%, nfe)

Conditions

MCADD - Medium-chain acyl-CoA dehydrogenase deficiency – full ACADM sequencing newborn screening follow up

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 4 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.91	GERP -0.32, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00186% European (non-Finnish) · 22/1,179,836 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00143% 23/1,613,730 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00186%	53,629
Remaining individualsnot grpmax-eligible	0.0016%	62,474

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.Trp82fs
Coding: c.244dup
MANE Select: NM_000016
dbSNP: rs786204566
Type: Duplication
Location: chr1:75732879 (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 82: an α-helix

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

Disease context

MCADD - Medium-chain acyl-CoA dehydrogenase deficiency – full ACADM sequencing newborn screening follow up

Also linked: medium chain acyl-CoA dehydrogenase deficiency

Similar variants

ACADM p.Trp82Ter Likely pathogenic ★ same residue
ACADM c.1194+1dup Likely pathogenic ★★ same condition
ACADM p.Ala372fs Pathogenic ★★ same condition
ACADM p.Gly115fs Pathogenic/Likely pathogenic ★★ same condition
ACADM p.Gly310fs Pathogenic/Likely pathogenic ★★ same condition
ACADM p.Ile78fs Pathogenic/Likely pathogenic ★★ same condition
ACADM p.Leu128fs Pathogenic/Likely pathogenic ★★ same condition
ACADM p.Ser38delinsArgIleTer 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/acadm-p-trp82fs (accessed [today's date]).

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