AARS1 p.Ala448=
c.1344C>T · rs920455151 · VCV699916
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
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 0.59 | GERP -2.2, phastCons 0.99 |
| Overall | ||
| CADD | 8.893 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,072 alleles
Filtering AF
0.00267%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00236%
Overall
0.00291%
47/1,613,638 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,072 |
| European (non-Finnish) | 0.00356% | 28,092 |
| Admixed American | 0.00334% | 29,976 |
| African / African-American | 0.00267% | 37,425 |
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.Ala448=
- Coding
- c.1344C>T
- MANE Select
- NM_001605
- dbSNP
- rs920455151
- Type
- single nucleotide variant
- Location
- chr16:70265541 (GRCh38)
- Gene constraint
- LOEUF 0.772 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 90.66 · 10 PDB
- Residue 448
- an α-helix
Similar variants
- 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
- AARS1 p.Arg333Ter Pathogenic/Likely pathogenic ★★ same condition
- AARS1 p.Arg598Ter 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-ala448 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown