GARS1 p.Pro703=
c.2109C>T · VCV4895564
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00534%, afr)
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 -0.88 | GERP -3.9 |
| Overall | ||
| CADD | 0.549 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00534%
African / African-American · 4/74,904 alleles
Filtering AF
0.00175%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00104%
Overall
0.00136%
22/1,613,908 alleles · very rare
exomes 19/1,461,776 · genomes 3/152,132 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00534% | 18,726 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,825 |
| Admixed American | 0.00167% | 60,004 |
| European (non-Finnish) | 0.00119% | 84,284 |
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
- GARS1
- Protein
- p.Pro703=
- Coding
- c.2109C>T
- MANE Select
- NM_002047
- Type
- single nucleotide variant
- Location
- chr7:30633749 (GRCh38)
- Gene constraint
- LOEUF 0.648 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.61 · 14 PDB
- Residue 703
- an α-helix
Similar variants
- GARS1 p.Pro703Leu Uncertain significance ★★ ⚠ 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-pro703 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown