GARS1 p.Ser635=
c.1905G>A · rs773889809 · VCV694995
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0329%, mid)
Conditions
2
Charcot-Marie-Tooth disease type 2
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.99 | acceptor gain · deltas |
|---|---|---|
| Pangolin | Δ0.78 | gain · loss 0.06 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 1.3 | GERP -3.9, phastCons 1 |
| Overall | ||
| CADD | 13.68 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0329%
Middle Eastern · 2/6,084 alleles
Filtering AF
0.0058%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00241%
Overall
0.00161%
26/1,613,816 alleles · ultra-rare
exomes 24/1,461,712 · genomes 2/152,104 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0329% | 3,042 |
| Admixed American | 0.005% | 19,993 |
| East Asian | 0.00223% | 44,896 |
| Finnishnot grpmax-eligible | 0.00156% | 64,008 |
| European (non-Finnish) | 0.00153% | 65,551 |
| South Asian | 0.0011% | 91,068 |
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.Ser635=
- Coding
- c.1905G>A
- MANE Select
- NM_002047
- dbSNP
- rs773889809
- Type
- single nucleotide variant
- Location
- chr7:30632248 (GRCh38)
- Gene constraint
- LOEUF 0.648 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.61 · 14 PDB
- Residue 635
- an α-helix; a UniProt-annotated variant site (has no effect on subcellular localization; results in decreased affinity for glycine)
Similar variants
- GARS1 p.Ser635Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- GARS1 p.Ser635Trp Uncertain significance ★ ⚠ same residue
- GARS1 p.Asp200Asn Pathogenic/Likely pathogenic ★★ same condition
- GARS1 p.Gly294Arg Pathogenic/Likely pathogenic ★★ same condition
- GARS1 p.Gly339Arg Pathogenic/Likely pathogenic ★★ same condition
- GARS1 p.His472Arg Pathogenic ★★ same condition
- GARS1 p.Ile334Asn Pathogenic/Likely pathogenic ★★ same condition
- GARS1 p.Ile334Phe Pathogenic ★★ same condition
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-ser635 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown