AGXT p.Arg375=
c.1125C>T · rs528663088 · VCV1097367
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.016%, sas)
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 -16 | GERP -2.5 |
| Overall | ||
| CADD | 0.123 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.016%
South Asian · 14/87,446 alleles
Filtering AF
0.00966%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00774%
Overall
0.00132%
21/1,593,302 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.016% | 6,246 |
| Remaining individualsnot grpmax-eligible | 0.00323% | 30,933 |
| Finnishnot grpmax-eligible | 0.00171% | 58,400 |
| European (non-Finnish) | 0.000341% | 293,370 |
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.Arg375=
- Coding
- c.1125C>T
- MANE Select
- NM_000030
- dbSNP
- rs528663088
- Type
- single nucleotide variant
- Location
- chr2:240878767 (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 375
- an α-helix
Similar variants
- AGXT p.Arg375His Uncertain significance ★ ⚠ 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-arg375 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown