Is ACADVL p.Arg366= (c.1098T>C) pathogenic?

ACADVL p.Arg366= (c.1098T>C) is classified Likely benign in ACADVL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-22). Very rare (popmax 6.84e-05%); Associated with very long chain acyl-CoA dehydrogenase deficiency.

What condition is associated with ACADVL p.Arg366= (c.1098T>C)?

ACADVL p.Arg366= (c.1098T>C) is associated with very long chain acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ACADVL p.Arg366= (c.1098T>C) in the general population?

ACADVL p.Arg366= (c.1098T>C) is very rare (popmax 6.84e-05%) (gnomAD).

ACADVL p.Arg366=

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.1098T>C · rs2142982087 · VCV1457662

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Conditions

very long 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 -0.18	GERP -0.06, phastCons 0.67
Overall
CADD	8.374	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.84e-05%

Overall 6.84e-05% 1/1,461,634 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: ACADVL
Protein: p.Arg366=
Coding: c.1098T>C
MANE Select: NM_000018
dbSNP: rs2142982087
Type: single nucleotide variant
Location: chr17:7223153 (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.Arg366Pro Likely pathogenic ★ 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-arg366 (accessed [today's date]).

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