PPA2 p.Ala130=
c.390G>A · rs776062584 · VCV1644385
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.033%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.045 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -5.3 | GERP -3.8 |
| Overall | ||
| CADD | 1.193 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.033%
Middle Eastern · 2/6,068 alleles
Filtering AF
0.00581%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00242%
Overall
0.000935%
15/1,604,930 alleles · ultra-rare
exomes 11/1,452,832 · genomes 4/152,098 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.033% | 3,034 |
| East Asian | 0.00904% | 11,057 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00339% | 29,456 |
| Admixed American | 0.00171% | 58,498 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,132 |
| African / African-American | 0.00134% | 74,514 |
| European (non-Finnish) | 0.000425% | 235,299 |
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.Ala130=
- Coding
- c.390G>A
- MANE Select
- NM_176869
- dbSNP
- rs776062584
- Type
- single nucleotide variant
- Location
- chr4:105446434 (GRCh38)
- Gene constraint
- LOEUF 1.324 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.39
Similar variants
- PPA2 p.Ala130Val Uncertain significance ★★ ⚠ same residue
- 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.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-ala130 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown