AGXT p.Leu143=
c.429G>A · rs375123832 · VCV718401
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00275%, nfe)
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 3 | GERP -1.5, phastCons 1 |
| Overall | ||
| CADD | 7.558 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00275%
European (non-Finnish) · 32/1,163,518 alleles
Filtering AF
0.00199%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0017%
Overall
0.00215%
34/1,579,386 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00275% | 36,360 |
| African / African-American | 0.0027% | 37,097 |
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.Leu143=
- Coding
- c.429G>A
- MANE Select
- NM_000030
- dbSNP
- rs375123832
- Type
- single nucleotide variant
- Location
- chr2:240871354 (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 143
- an α-helix
Similar variants
- 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
- AGXT c.596-2A>G 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-leu143 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown