GARS1 p.Pro298Arg
c.893C>G · VCV3602190
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.9995 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
3/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9995 | likely pathogenic ✓ concordant with ClinVar · top 2% in GARS1 |
|---|---|---|
| REVEL | 0.842 | moderately pathogenic-leaning |
| SaProt | LLR -14.67 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 0.97, phastCons 1 |
| Regional constraint | o/e 0.81 | unconstrained · MANE · 34 kb · p 2.2e-07 · regional, not allelic |
| Overall | ||
| CADD | 32.0 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- GARS1
- Protein
- p.Pro298Arg
- Coding
- c.893C>G
- MANE Select
- NM_002047
- Type
- single nucleotide variant
- Location
- chr7:30612107 (GRCh38)
- Gene constraint
- LOEUF 0.648 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.61 · 14 PDB
- Residue 298
- a UniProt-annotated variant site (in cmt2d; shows a large reduction in aminoacylation activity; demonstrates a change in subcellular location pattern; does not associate with granules); a β-strand
Similar variants
- GARS1 p.Pro298Leu Conflicting classifications of pathogenicity ⚠ same residue
- GARS1 p.Asp200Asn Pathogenic/Likely pathogenic ★★ same type
- GARS1 p.Gly294Arg Pathogenic/Likely pathogenic ★★ same type
- GARS1 p.Gly339Arg Pathogenic/Likely pathogenic ★★ same type
- GARS1 p.His472Arg Pathogenic ★★ same type
- GARS1 p.Ile334Asn Pathogenic/Likely pathogenic ★★ same type
- GARS1 p.Ile334Phe Pathogenic ★★ same type
- GARS1 p.Ile334Thr Pathogenic/Likely pathogenic ★★ 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/gars1-p-pro298arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown