Is ACADM p.Arg7= (c.21A>G) pathogenic?

ACADM p.Arg7= (c.21A>G) is classified Likely benign in ACADM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-10). Very rare (popmax 0.0038%, sas); Associated with medium chain acyl-CoA dehydrogenase deficiency.

What condition is associated with ACADM p.Arg7= (c.21A>G)?

ACADM p.Arg7= (c.21A>G) is associated with medium chain acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ACADM p.Arg7= (c.21A>G) in the general population?

ACADM p.Arg7= (c.21A>G) is very rare (popmax 0.0038%, sas) (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.Arg7=

c.21A>G · rs906559903 · VCV799225

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0038%, sas)

Conditions

medium chain acyl-CoA dehydrogenase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.324	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.085	GERP -2.9, phastCons 0.02
Overall
CADD	7.256	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0038% South Asian · 3/78,860 alleles

Filtering AF 0.00101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00048%

Overall 0.000857% 13/1,517,216 alleles · very rare exomes 10/1,365,058 · genomes 3/152,158 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0038%	26,287
Admixed American	0.00206%	48,608
African / African-American	0.00143%	69,894
European (non-Finnish)	0.000708%	141,222

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.Arg7=
Coding: c.21A>G
MANE Select: NM_000016
dbSNP: rs906559903
Type: single nucleotide variant
Location: chr1:75724808 (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.Arg7Ter Likely pathogenic ★ same residue
ACADM p.Arg7fs Likely pathogenic ★ same residue
ACADM p.Arg7Gln Uncertain significance ★ ⚠ same residue
ACADM c.118+1G>T Likely pathogenic ★★ same condition
ACADM c.1194+1G>A Pathogenic/Likely pathogenic ★★ same condition
ACADM c.1194+2T>G Likely pathogenic ★★ same condition
ACADM c.216+1G>A Pathogenic ★★ same condition
ACADM c.216+1G>T 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-arg7 (accessed [today's date]).

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