PRX p.His653Pro
c.1958A>C · VCV3310792
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely benign
0.1607 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/3 damaging
AlphaMissense, REVEL, SaProt
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| AlphaMissense | 0.1607 | likely benign |
|---|---|---|
| REVEL | 0.034 | moderately benign-leaning |
| SaProt | LLR -13.11 | damaging |
| ⇒ SaProt calls this damaging; AlphaMissense and REVEL do not. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -2.9 |
| Regional constraint | o/e 0.96 | unconstrained · MANE · 2,740 bp · p 0.15 · regional, not allelic |
| Overall | ||
| CADD | 0.005 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- PRX
- Protein
- p.His653Pro
- Coding
- c.1958A>C
- MANE Select
- NM_181882
- Type
- single nucleotide variant
- Location
- chr19:40396394 (GRCh38)
- Gene constraint
- LOEUF 1.321 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 35.74 · 1 PDB
- Residue 653
- the '55 x 5 aa approximate tandem repeats of [lvmag]-[psreqc]-[edkl]-[livmap]-[aqkhrpe]; that may have a tripeptide spacer of [lv]-p-[ker]' region
Similar variants
- PRX p.His653Arg Likely benign ★ same residue
- PRX p.His653Gln 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
- PRX p.Ala1074Thr 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-his653pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown