IARS2 p.Pro151=
c.453C>T · rs756654341 · VCV507136
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0317%, amr)
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 -4.1 | GERP -5.5 |
| Overall | ||
| CADD | 4.153 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0317%
Admixed American · 19/59,904 alleles
Filtering AF
0.0207%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0172%
Overall
0.00626%
101/1,612,800 alleles · ultra-rare
exomes 97/1,460,736 · genomes 4/152,064 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0317% | 3,153 |
| South Asian | 0.0154% | 6,496 |
| European (non-Finnish) | 0.00543% | 18,428 |
| Remaining individualsnot grpmax-eligible | 0.00481% | 20,805 |
| East Asian | 0.00223% | 44,774 |
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.Pro151=
- Coding
- c.453C>T
- MANE Select
- NM_018060
- dbSNP
- rs756654341
- Type
- single nucleotide variant
- Location
- chr1:220100552 (GRCh38)
- Gene constraint
- LOEUF 0.683 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.77
Similar variants
- 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
- IARS2 p.Ala701Val 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-pro151 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown