IARS1 p.Phe192=
c.576C>T · rs534075085 · VCV2176298
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.2%, sas)
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 -3.1 | GERP -2.8 |
| Overall | ||
| CADD | 8.177 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.2%
South Asian · 182/90,918 alleles
Filtering AF
0.176%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.167%
Overall
0.0131%
211/1,606,962 alleles · rare
exomes 201/1,454,696 · genomes 10/152,266 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.2% | 500 |
| East Asian | 0.0335% | 2,988 |
| Remaining individualsnot grpmax-eligible | 0.0145% | 6,918 |
| European (non-Finnish) | 0.000426% | 234,714 |
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
- IARS1
- Protein
- p.Phe192=
- Coding
- c.576C>T
- MANE Select
- NM_002161
- dbSNP
- rs534075085
- Type
- single nucleotide variant
- Location
- chr9:92285743 (GRCh38)
- Gene constraint
- LOEUF 0.911 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.06 · 1 PDB
Similar variants
- IARS1 p.Tyr71Ter Pathogenic ★★ same type
- IARS1 p.Ala222Gly Uncertain significance ★★ ⚠ same type
- IARS1 p.Ala325Thr Uncertain significance ★★ ⚠ same type
- IARS1 p.Ala485Val Uncertain significance ★★ ⚠ same type
- IARS1 p.Ala954Gly Uncertain significance ★★ ⚠ same type
- IARS1 p.Ala954Ser Uncertain significance ★★ ⚠ same type
- IARS1 p.Arg140Gln Uncertain significance ★★ ⚠ same type
- IARS1 p.Arg511Cys 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/iars1-p-phe192 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown