DARS2 p.Arg349fs
c.1046del · VCV3779562
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
leukoencephalopathy with brain stem and spinal cord involvement-high lactate syndrome
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 11 of 17 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 4 | GERP 0.31, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- DARS2
- Protein
- p.Arg349fs
- Coding
- c.1046del
- MANE Select
- NM_018122
- Type
- Deletion
- Location
- chr1:173840891 (GRCh38)
- Gene constraint
- LOEUF 0.923 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.91 · 1 PDB
Disease context
leukoencephalopathy with brain stem and spinal cord involvement-high lactate syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Leukoencephalopathy with brain stem and spinal cord involvement-high lactate syndrome (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Adolescent, Adult, Antenatal, Childhood, Infancy, Neonatal
Similar variants
- DARS2 p.Ala392fs Pathogenic/Likely pathogenic ★★ same condition
- DARS2 p.Gly365fs Likely pathogenic ★★ same condition
- DARS2 p.Gly467fs Pathogenic ★★ same condition
- DARS2 p.Leu187fs Pathogenic/Likely pathogenic ★★ same condition
- DARS2 p.Lys362fs Pathogenic/Likely pathogenic ★★ same condition
- DARS2 p.Pro317fs Pathogenic/Likely pathogenic ★★ same condition
- DARS2 c.228-10del Benign ★★ same condition
- DARS2 c.664-17_664-14del Likely benign ★★ 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/dars2-p-arg349fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown