DARS2 p.Arg58=
c.174T>G · VCV4760135
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00446%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.98 | GERP -3.2, phastCons 1 |
| Overall | ||
| CADD | 7.96 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00446%
East Asian · 2/44,880 alleles
Filtering AF
0.000875%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000443%
Overall
0.000372%
6/1,613,750 alleles · very rare
exomes 5/1,461,770 · genomes 1/151,980 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00446% | 22,440 |
| South Asian | 0.00329% | 30,356 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,496 |
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
- DARS2
- Protein
- p.Arg58=
- Coding
- c.174T>G
- MANE Select
- NM_018122
- Type
- single nucleotide variant
- Location
- chr1:173826733 (GRCh38)
- Gene constraint
- LOEUF 0.923 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.91 · 1 PDB
Similar variants
- DARS2 p.Arg58Gly Pathogenic/Likely pathogenic ★★ ⚠ same residue
- DARS2 p.Arg58His Conflicting classifications of pathogenicity ★ ⚠ same residue
- DARS2 c.228-15C>A Pathogenic/Likely pathogenic ★★ same type
- DARS2 c.228-16C>A Pathogenic/Likely pathogenic ★★ same type
- DARS2 c.397-2A>G Pathogenic/Likely pathogenic ★★ same type
- DARS2 c.492+2T>C Pathogenic ★★ same type
- DARS2 c.493-1G>C Likely pathogenic ★★ same type
- DARS2 p.Ala262Val Likely pathogenic ★★ same type
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-arg58 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown