Is ACADM p.Ala65= (c.195A>C) pathogenic?

ACADM p.Ala65= (c.195A>C) is classified Likely benign in ACADM (ClinVar, Single submitter, 2 submitters; last evaluated 2025-12-04). Very rare (popmax 0.00542%, nfe); Associated with medium chain acyl-CoA dehydrogenase deficiency.

What condition is associated with ACADM p.Ala65= (c.195A>C)?

ACADM p.Ala65= (c.195A>C) is associated with medium chain acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ACADM p.Ala65= (c.195A>C) in the general population?

ACADM p.Ala65= (c.195A>C) is very rare (popmax 0.00542%, 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.Ala65=

c.195A>C · rs771649282 · VCV697502

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00542%, 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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.002	GERP 0.35, phastCons 0.015
Overall
CADD	8.511	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00542% European (non-Finnish) · 64/1,179,884 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00396%

Overall 0.00409% 66/1,613,876 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00542%	18,436
Remaining individualsnot grpmax-eligible	0.0032%	31,233

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.Ala65=
Coding: c.195A>C
MANE Select: NM_000016
dbSNP: rs771649282
Type: single nucleotide variant
Location: chr1:75732720 (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 65: 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.Ala65fs 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
ACADM c.216+1G>T Pathogenic/Likely pathogenic ★★ same condition
ACADM c.216+2T>C Pathogenic ★★ same condition
ACADM c.216+2T>G 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-ala65 (accessed [today's date]).

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