ACADVL p.Val211fs
c.632_633del · rs1489679976 · VCV934787
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.632_633del (p.Val211GlyfsTer41)variant in ACADVL is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 9/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMIDs 9973285, 11590124). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). To our knowledge, this variant has not been reported in the literature in patients with ACADVL related disease or in functional studies. The ACADVL Variant Curation Expert Panel VCEP classified the variant as likely pathogenic based on PVS1+PM2_supporting. In summary, this variant meets the criteria to be classified as likely pathogenic 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: PMS2_Supporting, PVS1. (Required: VCEP specifications version 2.0; 1/14/22.)
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 8 of 20 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 1.4 | GERP -1.5, phastCons 0.78 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0011% | 91,084 |
| European (non-Finnish) | 0.000254% | 393,343 |
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.Val211fs
- Coding
- c.632_633del
- MANE Select
- NM_000018
- dbSNP
- rs1489679976
- Type
- Microsatellite
- Location
- chr17:7221959 (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 211
- 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.Val211= Likely benign ★★ same residue
- ACADVL p.Val211_Ala212insTer Likely pathogenic ★ same residue
- ACADVL p.Val211Ala Uncertain significance ★ ⚠ same residue
- ACADVL p.Arg286fs Likely pathogenic ★★★ same condition
- ACADVL p.Asp50fs Likely pathogenic ★★★ same condition
- ACADVL p.Gln100fs Pathogenic ★★★ same condition
- ACADVL p.Glu130del Pathogenic ★★★ same condition
- ACADVL p.Glu309fs 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-val211fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown