PPA2 p.Lys216=
c.648G>A · rs756410325 · VCV1933167
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00533%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.017 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -0.57 | GERP -3.3, phastCons 0.026 |
| Overall | ||
| CADD | 4.68 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00533%
Admixed American · 3/56,298 alleles
Filtering AF
0.00141%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000692%
Overall
0.000687%
11/1,601,226 alleles · very rare
exomes 10/1,449,060 · genomes 1/152,166 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00533% | 18,766 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 61,992 |
| European (non-Finnish) | 0.000595% | 168,164 |
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.Lys216=
- Coding
- c.648G>A
- MANE Select
- NM_176869
- dbSNP
- rs756410325
- Type
- single nucleotide variant
- Location
- chr4:105424203 (GRCh38)
- Gene constraint
- LOEUF 1.324 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.39
- Residue 216
- a modified residue (n6-succinyllysine)
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-lys216 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown