GARS1 p.Asp688=
c.2064C>T · rs528105619 · VCV1320985
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000339%, nfe)
Conditions
1
Charcot-Marie-Tooth disease type 2
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 1.1 | GERP 2, phastCons 1 |
| Overall | ||
| CADD | 9.479 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000339%
European (non-Finnish) · 4/1,180,020 alleles
Filtering AF
7.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.4e-05%
Overall
0.000248%
4/1,614,020 alleles · very rare
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.Asp688=
- Coding
- c.2064C>T
- MANE Select
- NM_002047
- dbSNP
- rs528105619
- Type
- single nucleotide variant
- Location
- chr7:30632407 (GRCh38)
- Gene constraint
- LOEUF 0.648 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.61 · 14 PDB
- Residue 688
- a β-strand
Similar variants
- GARS1 p.Asp688His 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
- GARS1 p.Ile334Thr Pathogenic/Likely 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-asp688 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown