AARS1 p.Arg476=
c.1428G>C · rs80257731 · VCV382360
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 9 submitters
gnomAD v4.1
Rare
rare (popmax 0.198%, mid)
Conditions
2
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 0.38 | GERP -0.22, phastCons 0.026 |
| Overall | ||
| CADD | 7.968 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.198%
Middle Eastern · 12/6,060 alleles
Filtering AF
0.114%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.102%
Overall
0.0383%
619/1,614,152 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.198% | 505 |
| Admixed American | 0.135% | 741 |
| Remaining individualsnot grpmax-eligible | 0.0608% | 1,645 |
| European (non-Finnish) | 0.0389% | 2,571 |
| African / African-American | 0.028% | 3,573 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00675% | 14,804 |
| South Asian | 0.00549% | 18,216 |
| Finnishnot grpmax-eligible | 0.00156% | 64,032 |
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
- AARS1
- Protein
- p.Arg476=
- Coding
- c.1428G>C
- MANE Select
- NM_001605
- dbSNP
- rs80257731
- Type
- single nucleotide variant
- Location
- chr16:70265022 (GRCh38)
- Gene constraint
- LOEUF 0.772 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 90.66 · 10 PDB
Similar variants
- AARS1 p.Arg476Gln Uncertain significance ★ ⚠ same residue
- AARS1 p.Arg476Trp Uncertain significance ★ ⚠ same residue
- AARS1 c.2177+1G>A Pathogenic/Likely pathogenic ★★ same condition
- AARS1 p.Arg13Ter Pathogenic ★★ same condition
- AARS1 p.Arg246Ter Pathogenic/Likely pathogenic ★★ same condition
- AARS1 p.Arg329Cys Likely pathogenic ★★ same condition
- AARS1 p.Arg329His Pathogenic/Likely pathogenic ★★ same condition
- AARS1 p.Arg330Ter 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/aars1-p-arg476 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown