IARS2 p.Pro247=
c.741G>A · rs199601961 · VCV753307
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.388%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.6 | GERP -5.8 |
| Overall | ||
| CADD | 9.619 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.388%
East Asian · 174/44,848 alleles
Filtering AF
0.341%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.323%
Overall
0.0159%
257/1,613,684 alleles · rare
exomes 223/1,461,422 · genomes 34/152,262 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.388% | 258 |
| South Asian | 0.0517% | 1,936 |
| Middle Eastern | 0.033% | 3,031 |
| Remaining individualsnot grpmax-eligible | 0.0288% | 3,471 |
| Admixed American | 0.005% | 19,986 |
| European (non-Finnish) | 0.0011% | 90,760 |
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.Pro247=
- Coding
- c.741G>A
- MANE Select
- NM_018060
- dbSNP
- rs199601961
- Type
- single nucleotide variant
- Location
- chr1:220102404 (GRCh38)
- Gene constraint
- LOEUF 0.683 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.77
Similar variants
- IARS2 p.Pro247Leu 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-pro247 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown