PPA2 p.Val186=
c.558G>A · rs143718058 · VCV1284796
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.103%, sas)
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 1.4 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 10.86 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.103%
South Asian · 91/88,072 alleles
Filtering AF
0.0861%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0797%
Overall
0.0151%
242/1,601,974 alleles · rare
exomes 214/1,449,744 · genomes 28/152,230 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.103% | 968 |
| Middle Eastern | 0.0993% | 1,007 |
| Remaining individualsnot grpmax-eligible | 0.0242% | 4,140 |
| Finnishnot grpmax-eligible | 0.0238% | 4,208 |
| Admixed American | 0.0176% | 5,677 |
| European (non-Finnish) | 0.00892% | 11,207 |
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.Val186=
- Coding
- c.558G>A
- MANE Select
- NM_176869
- dbSNP
- rs143718058
- Type
- single nucleotide variant
- Location
- chr4:105424293 (GRCh38)
- Gene constraint
- LOEUF 1.324 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.39
Similar variants
- PPA2 p.Val186Met 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 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-val186 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown