Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.0054%, nfe)
Conditions
3
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 2.2 | GERP -4.5, phastCons 1 |
| Overall | ||
| CADD | 5.719 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0054%
European (non-Finnish) · 62/1,148,608 alleles
Filtering AF
0.0043%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0039%
Overall
0.00415%
64/1,541,516 alleles · very rare
exomes 59/1,389,340 · genomes 5/152,176 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0054% | 18,526 |
| East Asian | 0.00242% | 41,252 |
| African / African-American | 0.00136% | 73,282 |
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
- PRX
- Protein
- p.Pro249=
- Coding
- c.747C>T
- MANE Select
- NM_181882
- dbSNP
- rs3814289
- Type
- single nucleotide variant
- Location
- chr19:40397605 (GRCh38)
- Gene constraint
- LOEUF 1.321 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 35.74 · 1 PDB
Similar variants
- PRX c.184+2T>C Likely pathogenic ★★ same condition
- PRX p.Arg1070Ter Pathogenic/Likely pathogenic ★★ same condition
- PRX p.Arg196Ter Pathogenic/Likely pathogenic ★★ same condition
- PRX p.Arg364Ter Pathogenic ★★ same condition
- PRX p.Arg368Ter Pathogenic/Likely pathogenic ★★ same condition
- PRX p.Arg392Ter Pathogenic/Likely pathogenic ★★ same condition
- PRX p.Arg464Ter Pathogenic/Likely pathogenic ★★ same condition
- PRX p.Arg897Ter Pathogenic/Likely pathogenic ★★ 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-pro249 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown