AGXT p.Ala40=
c.120C>T · rs1333685290 · VCV1124220
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0173%, mid)
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 -20 | GERP -2.5 |
| Overall | ||
| CADD | 0.214 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0173%
Middle Eastern · 1/5,778 alleles
Filtering AF
0.00295%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00262%
Overall
0.00313%
48/1,534,288 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0173% | 5,778 |
| European (non-Finnish) | 0.00389% | 25,730 |
| Remaining individualsnot grpmax-eligible | 0.0017% | 58,938 |
| African / African-American | 0.00149% | 67,008 |
| South Asian | 0.00113% | 88,282 |
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
- AGXT
- Protein
- p.Ala40=
- Coding
- c.120C>T
- MANE Select
- NM_000030
- dbSNP
- rs1333685290
- Type
- single nucleotide variant
- Location
- chr2:240868985 (GRCh38)
- Gene constraint
- LOEUF 1.251 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 98.30 · 17 PDB
- Residue 40
- an α-helix
Similar variants
- AGXT p.Ala40fs Pathogenic/Likely pathogenic ★★ same residue
- AGXT c.358+1G>A Pathogenic ★★ same type
- AGXT c.359-2A>G Likely pathogenic ★★ same type
- AGXT c.423+1G>A Pathogenic/Likely pathogenic ★★ same type
- AGXT c.524+2T>A Likely pathogenic ★★ same type
- AGXT c.525-1G>A Pathogenic ★★ same type
- AGXT c.525-2A>T Pathogenic/Likely pathogenic ★★ same type
- AGXT c.595+1G>T 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/agxt-p-ala40 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown