Is ACADVL p.Arg366Pro (c.1097G>C) pathogenic?

ACADVL p.Arg366Pro (c.1097G>C) is classified Likely pathogenic in ACADVL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-10). AlphaMissense: likely pathogenic (0.9941); Very rare (popmax 0.00223%, eas); Associated with very long chain acyl-CoA dehydrogenase deficiency.

What condition is associated with ACADVL p.Arg366Pro (c.1097G>C)?

ACADVL p.Arg366Pro (c.1097G>C) is associated with very long chain acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ACADVL p.Arg366Pro (c.1097G>C) in the general population?

ACADVL p.Arg366Pro (c.1097G>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about ACADVL p.Arg366Pro (c.1097G>C)?

AlphaMissense predicts likely pathogenic (score 0.9941) — an in-silico prediction, not a clinical call.

ACADVL p.Arg366Pro

Q: How is Very long chain acyl-CoA dehydrogenase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1097G>C · rs112406105 · VCV2707888

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9941 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

very long chain acyl-CoA dehydrogenase deficiency

Computational evidence

Protein change
AlphaMissense	0.9941	likely pathogenic ✓ concordant with ClinVar · top 2% in ACADVL
REVEL	0.98	strongly pathogenic-leaning
SaProt	LLR -16.52	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 5,109 bp · p 0.51 · regional, not allelic
Overall
CADD	33.0	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 0.00223% East Asian · 1/44,882 alleles

Overall 0.000137% 2/1,461,550 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,882
European (non-Finnish)	8.48e-05%	1,179,782

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: ACADVL
Protein: p.Arg366Pro
Coding: c.1097G>C
MANE Select: NM_000018
dbSNP: rs112406105
Type: single nucleotide variant
Location: chr17:7223152 (GRCh38)
Gene constraint: LOEUF 1.077 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.65 · 3 PDB
Residue 366: the 'catalytic' region; a UniProt-annotated variant site (in acadvld); a UniProt-annotated variant site (in acadvld; likely pathogenic)

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

Disease context

very long chain acyl-CoA dehydrogenase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Very long chain acyl-CoA dehydrogenase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

ACADVL p.Arg366Cys Likely pathogenic ★★★ same residue
ACADVL p.Arg366His Likely pathogenic ★★★ same residue
ACADVL p.Arg366Gly Likely pathogenic ★★ same residue
ACADVL p.Arg366Leu Likely pathogenic ★ same residue
ACADVL p.Arg366= Likely benign ★ same residue
ACADVL c.1077+1G>A Likely pathogenic ★★★ same condition
ACADVL c.1077+1G>T Likely pathogenic ★★★ same condition
ACADVL c.1077+2T>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/acadvl-p-arg366pro (accessed [today's date]).

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