PPA2 p.Glu326=
c.978G>A · rs1732949078 · VCV2102229
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00269%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.073 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -1.1 | GERP -1.4 |
| Overall | ||
| CADD | 4.257 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00269%
African / African-American · 2/74,214 alleles
Filtering AF
0.000447%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000167%
Overall
0.000189%
3/1,588,018 alleles · very rare
exomes 0/1,435,980 · genomes 3/152,038 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00269% | 37,107 |
| East Asian | 0.00224% | 44,742 |
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
- PPA2
- Protein
- p.Glu326=
- Coding
- c.978G>A
- MANE Select
- NM_176869
- dbSNP
- rs1732949078
- Type
- single nucleotide variant
- Location
- chr4:105369752 (GRCh38)
- Gene constraint
- LOEUF 1.324 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.39
Similar variants
- PPA2 p.Arg127Leu Pathogenic/Likely pathogenic ★★ ⚠ same type
- PPA2 p.Glu172Lys Pathogenic/Likely pathogenic ★★ same type
- PPA2 p.Pro228Leu Pathogenic/Likely pathogenic ★★ ⚠ same type
- PPA2 p.Thr159Met Pathogenic/Likely pathogenic ★★ ⚠ same type
- PPA2 c.528+1G>T Uncertain significance ★★ same type
- PPA2 p.Ala12Val Uncertain significance ★★ ⚠ same type
- PPA2 p.Ala130Val Uncertain significance ★★ ⚠ same type
- PPA2 p.Ala16Val 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/ppa2-p-glu326 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown