RARS1 p.Asp2=
c.6C>T · rs759568277 · VCV1680399
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00978%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>G here scores Δ0.63 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.008 | GERP -1.6, phastCons 0.6 |
| Overall | ||
| CADD | 7.134 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00978%
Admixed American · 5/51,134 alleles
Filtering AF
0.00381%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00247%
Overall
0.00154%
24/1,558,928 alleles · very rare
exomes 22/1,406,762 · genomes 2/152,166 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00978% | 10,227 |
| East Asian | 0.0071% | 14,082 |
| Finnishnot grpmax-eligible | 0.00498% | 20,083 |
| South Asian | 0.00236% | 42,339 |
| Remaining individualsnot grpmax-eligible | 0.00165% | 60,452 |
| European (non-Finnish) | 0.000869% | 115,061 |
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
- RARS1
- Protein
- p.Asp2=
- Coding
- c.6C>T
- MANE Select
- NM_002887
- dbSNP
- rs759568277
- Type
- single nucleotide variant
- Location
- chr5:168486504 (GRCh38)
- Gene constraint
- LOEUF 1.079 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.31 · 5 PDB
- Residue 2
- the 'could be involved in the assembly of the multisynthetase complex' region; a UniProt-annotated variant site (in hld9)
Similar variants
- RARS1 p.Asp2Gly Pathogenic/Likely pathogenic ★★ ⚠ same residue
- RARS1 p.Asp2_Val3delinsGluIle Pathogenic ★ same residue
- RARS1 c.1452+1G>A Pathogenic/Likely pathogenic ★★ same type
- RARS1 p.Ala439Asp Likely pathogenic ★★ same type
- RARS1 p.Arg512Gln Pathogenic/Likely pathogenic ★★ same type
- RARS1 p.Arg59Ter Pathogenic/Likely pathogenic ★★ same type
- RARS1 p.Met1Lys Pathogenic ★★ same type
- RARS1 p.Met1Thr 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/rars1-p-asp2 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown