PPA2 c.976+232G>A
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 43.3%, eas) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +232 | deep intronic (+232 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.15 | GERP 0.15 |
| Non-coding constraint | Z 0.84 | 1 kb window · o/e 0.93 · regional · uncalibrated |
| Overall | ||
| CADD | 5.245 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
43.3%
East Asian · 3,741/8,636 alleles
Filtering AF
42.2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 41.7%
Overall
23.5%
228,235/970,802 alleles · common
exomes 190,305/819,704 · genomes 37,930/151,098 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 43.3% | 2 |
| Admixed American | 29.7% | 3 |
| Remaining individualsnot grpmax-eligible | 24.9% | 4 |
| African / African-American | 24% | 4 |
| European (non-Finnish) | 23.2% | 4 |
| Middle Eastern | 22.9% | 4 |
| Ashkenazi Jewishnot grpmax-eligible | 22.8% | 4 |
| South Asian | 21.5% | 5 |
| Finnishnot grpmax-eligible | 20.8% | 5 |
| Amishnot grpmax-eligible | 18.1% | 6 |
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
- Coding
- c.976+232G>A
- MANE Select
- NM_176869
- dbSNP
- rs36112402
- Type
- single nucleotide variant
- Location
- chr4:105370605 (GRCh38)
- Gene constraint
- LOEUF 1.324 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.39
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-c-976-plus-232g-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown