YARS1 p.Pro342=
c.1026A>G · rs2523359284 · VCV3045241
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0011%, sas)
Conditions
1
YARS1-related disorder
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 0.4 | GERP -1.5, phastCons 1 |
| Overall | ||
| CADD | 9.343 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0011%
South Asian · 1/91,072 alleles
Filtering AF
0.000124%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9e-05%
Overall
0.000372%
6/1,614,014 alleles · very rare
exomes 6/1,461,740 · genomes 0/152,274 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0011% | 91,072 |
| European (non-Finnish) | 0.000424% | 235,982 |
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
- YARS1
- Protein
- p.Pro342=
- Coding
- c.1026A>G
- MANE Select
- NM_003680
- dbSNP
- rs2523359284
- Type
- single nucleotide variant
- Location
- chr1:32782420 (GRCh38)
- Gene constraint
- LOEUF 0.734 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 91.12 · 8 PDB
- Residue 342
- the 'disordered' region
Disease context
YARS1-related disorder
Similar variants
- YARS1 p.Pro167Thr Pathogenic/Likely pathogenic ★★ same condition
- YARS1 p.Glu196Gln Pathogenic/Likely pathogenic ★★ same type
- YARS1 p.Glu196Lys Pathogenic/Likely pathogenic ★★ same type
- YARS1 c.1042+3A>C Uncertain significance ★★ same type
- YARS1 c.58-2A>G Uncertain significance ★★ same type
- YARS1 c.*539A>G Uncertain significance ★★ same type
- YARS1 p.Ala181Asp Uncertain significance ★★ ⚠ same type
- YARS1 p.Ala384Thr 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/yars1-p-pro342 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown