IARS2 p.Pro314=
c.942T>C · rs148564492 · VCV382998
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.08%, afr)
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 -0.87 | GERP -5.8 |
| Overall | ||
| CADD | 4.023 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.08%
African / African-American · 811/74,786 alleles
Filtering AF
1.02%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.998%
Overall
0.054%
865/1,601,148 alleles · low-frequency
exomes 441/1,448,790 · genomes 424/152,358 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.08% | 92 |
| Remaining individualsnot grpmax-eligible | 0.0564% | 1,773 |
| Admixed American | 0.025% | 4,001 |
| South Asian | 0.0011% | 90,776 |
| European (non-Finnish) | 0.000257% | 389,440 |
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.Pro314=
- Coding
- c.942T>C
- MANE Select
- NM_018060
- dbSNP
- rs148564492
- Type
- single nucleotide variant
- Location
- chr1:220102769 (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-pro314 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown