ACADVL p.Ser418fs
c.1251del · rs2142984544 · VCV1073505
ClinGen expert panel — ACADVL VCEP
Likely Pathogenic for very long chain acyl-CoA dehydrogenase deficiency. Applied ACMG criteria (verbatim):
PVS1 PM2_Supporting
Curation rationale (ClinGen, verbatim)
The c.1251del (p.Ser418fs) also known as (p.Ser418AlafsTer12) variant in ACADVL is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 12/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMIDs 9973285, 11590124). To our knowledge, this variant has not been reported in the literature in any individuals with very long chain acyl-CoA dehydrogenase (VLCAD) deficiency. Additionally, to our knowledge, functional assays have not been reported for this variant. This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, this variant meets the criteria to be classified as likely pathogenic for autosomal recessive VLCAD deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen ACADVL Variant Curation Expert Panel: PVS1, PM2_Supporting (VCEP specifications version1; approved November 8, 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. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 12 of 20 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 7.9 | GERP 2.1, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.
Variant & gene context
- Gene
- ACADVL
- Protein
- p.Ser418fs
- Coding
- c.1251del
- MANE Select
- NM_000018
- dbSNP
- rs2142984544
- Type
- Deletion
- Location
- chr17:7223712 (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 418
- an α-helix; the 'catalytic' region
Disease context
very long chain acyl-CoA dehydrogenase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Very long chain acyl-CoA dehydrogenase deficiency (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Infancy, Neonatal
- Prevalence
- 1-9 / 100 000 (Europe)
Similar variants
- ACADVL p.Ser418Asn Pathogenic ★ same residue
- ACADVL p.Ser418Arg Uncertain significance ★ ⚠ same residue
- ACADVL p.Ser418Thr Uncertain significance ★ ⚠ same residue
- ACADVL c.1606-3_1606-2del Pathogenic ★★★ same condition
- ACADVL c.1752-3_1755del Pathogenic ★★★ same condition
- ACADVL c.343del Pathogenic ★★★ same condition
- ACADVL p.Ala347fs Likely pathogenic ★★★ same condition
- ACADVL p.Ala544fs Likely 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-ser418fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown