GPI p.Pro409=
c.1227G>A · rs774225651 · VCV1347400
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.005%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.41 | acceptor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -9 | GERP -4.8 |
| Overall | ||
| CADD | 13.74 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.005%
Admixed American · 3/60,020 alleles
Filtering AF
0.00133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000668%
Overall
0.000991%
16/1,614,120 alleles · very rare
exomes 16/1,461,862 · genomes 0/152,258 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.005% | 20,007 |
| Finnishnot grpmax-eligible | 0.00469% | 21,343 |
| African / African-American | 0.00133% | 75,038 |
| European (non-Finnish) | 0.000763% | 131,113 |
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
- GPI
- Protein
- p.Pro409=
- Coding
- c.1227G>A
- MANE Select
- NM_000175
- dbSNP
- rs774225651
- Type
- single nucleotide variant
- Location
- chr19:34396615 (GRCh38)
- Structure
- AlphaFold pLDDT 93.81 · 1 PDB
Similar variants
- GPI p.Ala337Thr Pathogenic/Likely pathogenic ★★ ⚠ same type
- GPI p.Arg347Cys Pathogenic/Likely pathogenic ★★ same type
- GPI p.Arg347His Pathogenic/Likely pathogenic ★★ ⚠ same type
- GPI p.Arg446Ter Pathogenic/Likely pathogenic ★★ same type
- GPI p.Arg472Cys Pathogenic ★★ ⚠ same type
- GPI p.Arg96Ter Pathogenic/Likely pathogenic ★★ same type
- GPI p.Gln343Arg Pathogenic/Likely pathogenic ★★ same type
- GPI c.909+5G>A 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/gpi-p-pro409 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown