DARS2 p.Ala460=
c.1380T>C · rs374131923 · VCV1939399
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00347%, nfe)
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 -2.3 | GERP -4.2 |
| Overall | ||
| CADD | 5.044 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00347%
European (non-Finnish) · 41/1,180,036 alleles
Filtering AF
0.00259%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00233%
Overall
0.0026%
42/1,613,938 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00347% | 28,781 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,474 |
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.Ala460=
- Coding
- c.1380T>C
- MANE Select
- NM_018122
- dbSNP
- rs374131923
- Type
- single nucleotide variant
- Location
- chr1:173853384 (GRCh38)
- Gene constraint
- LOEUF 0.923 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.91 · 1 PDB
Similar variants
- 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
- DARS2 p.Arg179His Pathogenic/Likely pathogenic ★★ same type
- DARS2 p.Arg188Ter Pathogenic/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-ala460 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown