PPA2 p.Leu8=
c.22C>T · rs201219272 · VCV1594375
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00694%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 5.3 | GERP -1.8, phastCons 1 |
| Overall | ||
| CADD | 7.237 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00694%
Admixed American · 4/57,618 alleles
Filtering AF
0.00232%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00139%
Overall
0.000314%
5/1,592,624 alleles · very rare
exomes 5/1,440,352 · genomes 0/152,272 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00694% | 14,405 |
| Remaining individualsnot grpmax-eligible | 0.00163% | 61,456 |
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.Leu8=
- Coding
- c.22C>T
- MANE Select
- NM_176869
- dbSNP
- rs201219272
- Type
- single nucleotide variant
- Location
- chr4:105474029 (GRCh38)
- Gene constraint
- LOEUF 1.324 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.39
Similar variants
- PPA2 p.Leu8Arg 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.Ala130Val 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-leu8 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown