Is ACADM p.Arg349Ter (c.1045C>T) pathogenic?

ACADM p.Arg349Ter (c.1045C>T) is classified Pathogenic in ACADM (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-08). Very rare (popmax 0.00667%, afr); Associated with medium chain acyl-CoA dehydrogenase deficiency.

What condition is associated with ACADM p.Arg349Ter (c.1045C>T)?

ACADM p.Arg349Ter (c.1045C>T) is associated with medium chain acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ACADM p.Arg349Ter (c.1045C>T) in the general population?

ACADM p.Arg349Ter (c.1045C>T) is very rare (popmax 0.00667%, afr) (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.Arg349Ter

c.1045C>T · rs148207467 · VCV189016

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

Conditions

medium chain acyl-CoA dehydrogenase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 11 of 12
Splicing
SpliceAI	Δ0.29	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 0.38	GERP -0.12, phastCons 0.025
Overall
CADD	41.0	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 0.00667% African / African-American · 5/74,992 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.000929% 15/1,614,038 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00667%	14,998
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602
South Asian	0.0022%	45,538
Admixed American	0.00167%	60,010
European (non-Finnish)	0.000508%	196,668

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.Arg349Ter
Coding: c.1045C>T
MANE Select: NM_000016
dbSNP: rs148207467
Type: single nucleotide variant
Location: chr1:75761221 (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.Arg349Gly Pathogenic ★ ⚠ same residue
ACADM p.Arg349Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
ACADM p.Arg349Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
ACADM p.Arg349fs Likely pathogenic ★ 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

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-arg349ter (accessed [today's date]).

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