PPA2 p.Thr159=
c.477G>A · rs139651138 · VCV1272569
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.42%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.038 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.25 | GERP -2.4 |
| Overall | ||
| CADD | 7.699 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.42%
European (non-Finnish) · 28,458/1,178,042 alleles
Filtering AF
2.39%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.38%
Overall
1.93%
31,030/1,607,366 alleles · low-frequency
exomes 29,198/1,455,152 · genomes 1,832/152,214 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 2.42% | 41 |
| Remaining individualsnot grpmax-eligible | 1.57% | 64 |
| Admixed American | 0.874% | 114 |
| Finnishnot grpmax-eligible | 0.653% | 153 |
| Middle Eastern | 0.58% | 172 |
| Ashkenazi Jewishnot grpmax-eligible | 0.432% | 232 |
| African / African-American | 0.36% | 278 |
| South Asian | 0.263% | 380 |
| Amishnot grpmax-eligible | 0.219% | 456 |
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.Thr159=
- Coding
- c.477G>A
- MANE Select
- NM_176869
- dbSNP
- rs139651138
- Type
- single nucleotide variant
- Location
- chr4:105438001 (GRCh38)
- Gene constraint
- LOEUF 1.324 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.39
Similar variants
- PPA2 p.Thr159Met Pathogenic/Likely pathogenic ★★ ⚠ 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 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-thr159 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown