IARS2 p.Arg6=
c.18C>T · rs1251807135 · VCV3001421
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00339%, sas)
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 -0.61 | GERP -2.8 |
| Overall | ||
| CADD | 9.929 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00339%
South Asian · 3/88,464 alleles
Filtering AF
0.000901%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00045%
Overall
0.000314%
5/1,591,202 alleles · very rare
exomes 5/1,438,864 · genomes 0/152,338 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00339% | 29,488 |
| Admixed American | 0.00174% | 57,384 |
| Remaining individualsnot grpmax-eligible | 0.00163% | 61,288 |
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
- IARS2
- Protein
- p.Arg6=
- Coding
- c.18C>T
- MANE Select
- NM_018060
- dbSNP
- rs1251807135
- Type
- single nucleotide variant
- Location
- chr1:220094234 (GRCh38)
- Gene constraint
- LOEUF 0.683 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.77
Similar variants
- IARS2 p.Arg6Cys Uncertain significance ★★ ⚠ same residue
- IARS2 p.Arg817His Pathogenic/Likely pathogenic ★★ ⚠ same type
- IARS2 p.Tyr117Ter Pathogenic/Likely pathogenic ★★ same type
- IARS2 c.550+6T>A Uncertain significance ★★ same type
- IARS2 p.Ala12Thr Uncertain significance ★★ ⚠ same type
- IARS2 p.Ala338Val Uncertain significance ★★ ⚠ same type
- IARS2 p.Ala492Val Uncertain significance ★★ ⚠ same type
- IARS2 p.Ala587Thr Uncertain significance ★★ ⚠ 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/iars2-p-arg6 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown