ACADVL p.Arg341Thr
c.1022G>C · rs1064793382 · VCV418711
ClinGen expert panel — ACADVL VCEP
Uncertain Significance for very long chain acyl-CoA dehydrogenase deficiency. Applied ACMG criteria (verbatim):
PM2_Supporting PP3
Curation rationale (ClinGen, verbatim)
The c.1022G>C (NM_000018.4) variant in ACADVL is a missense variant predicted to cause substitution of arginine by threonine at amino acid 341 (p.Arg341Thr). To our knowledge, this variant is not reported in the medical literature. This variant is absent from gnomAD v2.1.1 (PM2_Supporting). The computational predictor REVEL gives a score of 0.971, which is above the threshold of 0.75, evidence that correlates with impact to ACADVL function (PP3). In summary, this variant meets the criteria to be classified as 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: PM2_Supporting, PP3 (ACADVL VCEP specifications version 1; approved November 9, 2021).
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9983 | likely pathogenic · top 1% in ACADVL |
|---|---|---|
| REVEL | 0.971 | strongly pathogenic-leaning |
| SaProt | LLR -12.60 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 1.9, phastCons 1 |
| Regional constraint | o/e 1.02 | unconstrained · MANE · 5,109 bp · p 0.51 · regional, not allelic |
| Overall | ||
| CADD | 32.0 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- ACADVL
- Protein
- p.Arg341Thr
- Coding
- c.1022G>C
- MANE Select
- NM_000018
- dbSNP
- rs1064793382
- Type
- single nucleotide variant
- Location
- chr17:7222810 (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 341
- 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.Arg341= Likely benign ★ 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
- ACADVL c.1077+2T>C Pathogenic ★★★ same condition
- ACADVL c.1182+1G>A Likely pathogenic ★★★ same condition
- ACADVL c.1269+1G>A Likely pathogenic ★★★ same condition
- ACADVL c.1532+1G>A 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-arg341thr (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown