PRX p.Arg1375=
c.4125G>A · VCV3784179
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0241%, afr)
Conditions
1
Inborn genetic diseases
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 -2 | GERP -2.2 |
| Overall | ||
| CADD | 1.081 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0241%
African / African-American · 18/74,712 alleles
Filtering AF
0.0155%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0129%
Overall
0.00119%
19/1,602,994 alleles · ultra-rare
exomes 8/1,450,858 · genomes 11/152,136 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0241% | 4,151 |
| South Asian | 0.00111% | 90,252 |
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
- PRX
- Protein
- p.Arg1375=
- Coding
- c.4125G>A
- MANE Select
- NM_181882
- Type
- single nucleotide variant
- Location
- chr19:40394227 (GRCh38)
- Gene constraint
- LOEUF 1.321 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 35.74 · 1 PDB
- Residue 1375
- the 'disordered' region
Similar variants
- PRX p.Arg1375Gln Uncertain significance ★★ ⚠ same residue
- PRX p.Arg1375Leu Uncertain significance ★ ⚠ same residue
- PRX p.Arg1375Trp Uncertain significance ★ ⚠ same residue
- PRX c.184+2T>C Likely pathogenic ★★ same condition
- PRX p.Arg368Ter Pathogenic/Likely pathogenic ★★ same condition
- PRX p.Cys715Ter Pathogenic/Likely pathogenic ★★ same condition
- PRX p.Tyr77Ter Pathogenic ★★ same condition
- PRX p.Ala1036Val Uncertain significance ★★ ⚠ 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/prx-p-arg1375 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown