Is ACADM p.Ala205Pro (c.613G>C) pathogenic?

ACADM p.Ala205Pro (c.613G>C) is classified Pathogenic/Likely pathogenic in ACADM (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-10). AlphaMissense: likely pathogenic (0.9883); Very rare (popmax 8.48e-05%, nfe); Associated with medium chain acyl-CoA dehydrogenase deficiency.

What condition is associated with ACADM p.Ala205Pro (c.613G>C)?

ACADM p.Ala205Pro (c.613G>C) is associated with medium chain acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ACADM p.Ala205Pro (c.613G>C) in the general population?

ACADM p.Ala205Pro (c.613G>C) is very rare (popmax 8.48e-05%, 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.

What do computational predictors say about ACADM p.Ala205Pro (c.613G>C)?

AlphaMissense predicts likely pathogenic (score 0.9883) — an in-silico prediction, not a clinical call.

ACADM p.Ala205Pro

c.613G>C · rs1324329442 · VCV1455130

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9883 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

medium chain acyl-CoA dehydrogenase deficiency

Computational evidence

Protein change
AlphaMissense	0.9883	likely pathogenic ✓ concordant with ClinVar · top 7% in ACADM
REVEL	0.961	strongly pathogenic-leaning
SaProt	LLR -16.05	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.42 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 38 kb · p 0.63 · regional, not allelic
Overall
CADD	29.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,364 alleles

Overall 6.84e-05% 1/1,461,066 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.Ala205Pro
Coding: c.613G>C
MANE Select: NM_000016
dbSNP: rs1324329442
Type: single nucleotide variant
Location: chr1:75745819 (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 205: a β-strand

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.Ala205Val Conflicting classifications of pathogenicity ★ ⚠ same residue
ACADM p.Ala205= Likely benign ★ 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

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-ala205pro (accessed [today's date]).

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