PLA2G4A p.Pro586=
c.1758G>A · rs34758865 · VCV721606
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.78%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -8 | GERP -5.1 |
| Overall | ||
| CADD | 0.487 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.78%
African / African-American · 584/74,898 alleles
Filtering AF
0.727%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.707%
Overall
0.0434%
698/1,607,886 alleles · rare
exomes 338/1,455,646 · genomes 360/152,240 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.78% | 128 |
| Remaining individualsnot grpmax-eligible | 0.0578% | 1,730 |
| Admixed American | 0.05% | 2,000 |
| Middle Eastern | 0.0331% | 3,023 |
| South Asian | 0.00659% | 15,163 |
| European (non-Finnish) | 0.00324% | 30,905 |
| East Asian | 0.00223% | 44,832 |
| Finnishnot grpmax-eligible | 0.00156% | 63,996 |
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
- PLA2G4A
- Protein
- p.Pro586=
- Coding
- c.1758G>A
- MANE Select
- NM_024420
- dbSNP
- rs34758865
- Type
- single nucleotide variant
- Location
- chr1:186965587 (GRCh38)
- Gene constraint
- LOEUF 0.89 · pLI 0.19 (gnomAD)
- Structure
- AlphaFold pLDDT 84.15 · 3 PDB
- Residue 586
- the pla2c domain
Similar variants
- PLA2G4A p.Ala34Thr Uncertain significance ★★ ⚠ same type
- PLA2G4A p.Ala364Thr Uncertain significance ★★ ⚠ same type
- PLA2G4A p.Met209Thr Uncertain significance ★★ ⚠ same type
- PLA2G4A p.Met468Val Uncertain significance ★★ ⚠ same type
- PLA2G4A p.Met470Val Uncertain significance ★★ ⚠ same type
- PLA2G4A p.Pro656Ser Uncertain significance ★★ ⚠ same type
- PLA2G4A c.115+13T>A Benign/Likely benign ★★ same type
- PLA2G4A c.115+7G>A Likely benign ★★ 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/pla2g4a-p-pro586 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown