PRUNE1 p.Pro409=
c.1227G>A · rs193222748 · VCV2083106
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0767%, amr)
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 -4.6 | GERP -3.7 |
| Overall | ||
| CADD | 6.856 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0767%
Admixed American · 46/60,006 alleles
Filtering AF
0.059%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0528%
Overall
0.0102%
165/1,614,098 alleles · ultra-rare
exomes 122/1,461,868 · genomes 43/152,230 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0767% | 1,304 |
| Remaining individualsnot grpmax-eligible | 0.0224% | 4,465 |
| European (non-Finnish) | 0.00839% | 11,919 |
| African / African-American | 0.004% | 25,005 |
| South Asian | 0.00329% | 30,357 |
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
- PRUNE1
- Protein
- p.Pro409=
- Coding
- c.1227G>A
- MANE Select
- NM_021222
- dbSNP
- rs193222748
- Type
- single nucleotide variant
- Location
- chr1:151034099 (GRCh38)
- Gene constraint
- LOEUF 0.902 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.61
- Residue 409
- the 'essential for homodimerization' region; the 'disordered' region; a UniProt-annotated variant site (in nmihba)
Similar variants
- PRUNE1 c.132+2T>C Pathogenic ★★ same type
- PRUNE1 c.521-2A>G Pathogenic/Likely pathogenic ★★ same type
- PRUNE1 p.Arg128Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
- PRUNE1 p.Arg66Ter Pathogenic/Likely pathogenic ★★ same type
- PRUNE1 p.Asp106Asn Pathogenic/Likely pathogenic ★★ same type
- PRUNE1 p.Asp30Asn Pathogenic/Likely pathogenic ★★ same type
- PRUNE1 p.Ala39Pro Uncertain significance ★★ ⚠ same type
- PRUNE1 p.Asp87Asn 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/prune1-p-pro409 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown