PXDN p.Pro225=
c.675C>T · VCV4951742
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0156%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.133 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -2.6 | GERP -2 |
| Overall | ||
| CADD | 1.962 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0156%
East Asian · 7/44,804 alleles
Filtering AF
0.00727%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00515%
Overall
0.000558%
9/1,612,080 alleles · ultra-rare
exomes 7/1,459,918 · genomes 2/152,162 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0156% | 6,401 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,424 |
| European (non-Finnish) | 8.48e-05% | 1,179,204 |
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
- PXDN
- Protein
- p.Pro225=
- Coding
- c.675C>T
- MANE Select
- NM_012293
- Type
- single nucleotide variant
- Location
- chr2:1680248 (GRCh38)
- Gene constraint
- LOEUF 0.677 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.43
- Residue 225
- the lrrct domain
Similar variants
- PXDN p.Ala211Val Uncertain significance ★★ ⚠ same type
- PXDN p.Arg1242Cys Uncertain significance ★★ ⚠ same type
- PXDN p.Arg1376Cys Uncertain significance ★★ ⚠ same type
- PXDN p.Arg372Gln Uncertain significance ★★ ⚠ same type
- PXDN p.Arg597Trp Uncertain significance ★★ same type
- PXDN p.Arg84Gln Uncertain significance ★★ ⚠ same type
- PXDN p.Arg874Cys Uncertain significance ★★ ⚠ same type
- PXDN p.Asn655Ser Uncertain significance ★★ ⚠ 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/pxdn-p-pro225 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown