Is ACADVL p.Arg613= (c.1839G>A) pathogenic?

ACADVL p.Arg613= (c.1839G>A) is classified Likely benign in ACADVL (ClinVar, Expert panel, 11 submitters; last evaluated 2025-04-22). Rare (popmax 0.823%, afr); Associated with very long chain acyl-CoA dehydrogenase deficiency.

What condition is associated with ACADVL p.Arg613= (c.1839G>A)?

ACADVL p.Arg613= (c.1839G>A) is associated with very long chain acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ACADVL p.Arg613= (c.1839G>A) in the general population?

ACADVL p.Arg613= (c.1839G>A) is rare (popmax 0.823%, afr) (gnomAD).

ACADVL p.Arg613=

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.1839G>A · rs79125791 · VCV254698

Likely benign Expert panel

Classification

Likely benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 11 submitters

gnomAD v4.1

Rare

rare (popmax 0.823%, afr)

Conditions

very long chain acyl-CoA dehydrogenase deficiency

ClinGen expert panel — ACADVL VCEP

Likely Benign for very long chain acyl-CoA dehydrogenase deficiency. Applied ACMG criteria (verbatim):

PM2_Supporting BP7 BP4

Curation rationale (ClinGen, verbatim)

The c.1839G>A p.(Arg613=) variant is a synonymous (silent) variant that is not predicted by SpliceAI to impact splicing. In addition, it occurs at a nucleotide that is not conserved as shown by PhyloP100way (conservation score: 0.95) (BP4, BP7). The highest population minor allele frequency in gnomAD v2.1.1 is 0.008134 in African/African American population, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) for PM2_Supporting; however, this is not considered conflicting evidence with BP4 and BP7. To our knowledge, this variant has not been reported in the literature in any individuals with autosomal recessive very long chain acyl-CoA dehydrogenase (VLCAD) deficiency. In summary, this variant meets the criteria to be classified as likely benign for autosomal recessive very long chain acyl-CoA dehydrogenase (VLCAD) deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen ACADVL Variant Curation Expert Panel: BP4, BP7, PM2_Supporting (ACADVL VCEP specifications version 1; approved November 9, 2021).

ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.

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 0.96	GERP -0.21, phastCons 1
Overall
CADD	6.988	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.823% African / African-American · 618/75,052 alleles

Filtering AF 0.77% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.748%

Overall 0.0451% 728/1,614,102 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.823%	121
Middle Eastern	0.412%	242
Admixed American	0.055%	1,819
Remaining individualsnot grpmax-eligible	0.0528%	1,894
European (non-Finnish)	0.00153%	65,557
South Asian	0.0011%	91,088

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.Arg613=
Coding: c.1839G>A
MANE Select: NM_000018
dbSNP: rs79125791
Type: single nucleotide variant
Location: chr17:7224968 (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 613: an α-helix; 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.Arg613Trp Likely pathogenic ★★★ same residue
ACADVL p.Arg613Pro Pathogenic ★★ same residue
ACADVL p.Arg613Leu Likely pathogenic ★ same residue
ACADVL p.Arg613Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
ACADVL p.Arg613Gln Pathogenic/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-arg613 (accessed [today's date]).

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