ACADVL p.Cys603fs
c.1808del · rs2142990894 · VCV1075156
ClinGen expert panel — ACADVL VCEP
Uncertain Significance for very long chain acyl-CoA dehydrogenase deficiency. Applied ACMG criteria (verbatim):
PVS1_Moderate PM2_Supporting
Curation rationale (ClinGen, verbatim)
The c.1808del (p.Cys603fs) variant in ACADVL, also known as p.Cys603LeufsTer77, is a frameshift variant that may cause loss of function of the protein; however it is predicted to escape nonsense mediated decay and remove <10% of the protein (PVS1_Moderate). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). Due to limited evidence, this variant is classified as a variant of uncertain significance 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: PVS1_Moderate, PM2_Supporting (ACADVL VCEP specifications version 1; 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 | escapes | premature termination codon within the last 50 nt of the penultimate exon (19 of 20, 19 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 7.8 | GERP 2.2, 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.Cys603fs
- Coding
- c.1808del
- MANE Select
- NM_000018
- dbSNP
- rs2142990894
- Type
- Deletion
- Location
- chr17:7224865 (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 603
- an α-helix
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.Cys603Arg 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
- ACADVL p.Ala577fs Likely pathogenic ★★★ same condition
- ACADVL p.Arg512fs 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-cys603fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown