AARS2 p.Ala44=
c.132C>T · rs756852994 · VCV386053
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00331%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.7 | GERP 0.84, phastCons 1 |
| Overall | ||
| CADD | 11.98 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00331%
European (non-Finnish) · 39/1,179,206 alleles
Filtering AF
0.00248%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00217%
Overall
0.00255%
41/1,610,856 alleles · very rare
exomes 39/1,458,590 · genomes 2/152,266 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00331% | 30,236 |
| Admixed American | 0.00167% | 59,728 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,308 |
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
- AARS2
- Protein
- p.Ala44=
- Coding
- c.132C>T
- MANE Select
- NM_020745
- dbSNP
- rs756852994
- Type
- single nucleotide variant
- Location
- chr6:44313192 (GRCh38)
- Gene constraint
- LOEUF 0.752 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 88.05 · 3 PDB
Similar variants
- AARS2 c.2146-2A>G Pathogenic/Likely pathogenic ★★ same type
- AARS2 c.2255+1G>A Pathogenic ★★ same type
- AARS2 c.2598+1G>T Pathogenic/Likely pathogenic ★★ same type
- AARS2 p.Arg199Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
- AARS2 p.Arg521Ter Pathogenic ★★ same type
- AARS2 p.Arg580Trp Likely pathogenic ★★ ⚠ same type
- AARS2 p.Arg592Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
- AARS2 p.Arg958Ter 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/aars2-p-ala44 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown