PPA2 c.976+246del
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 42.6%, 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 +246 | deep intronic (+246 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -0.99 | GERP -1.8 |
| Non-coding constraint | Z 0.84 | 1 kb window · o/e 0.93 · regional · uncalibrated |
| Overall | ||
| CADD | 0.544 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
42.6%
East Asian · 3,651/8,572 alleles
Filtering AF
41.4%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 41%
Overall
10.7%
103,302/961,456 alleles · common
exomes 84,035/814,432 · genomes 19,267/147,024 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 42.6% | 2 |
| Admixed American | 19.5% | 5 |
| Middle Eastern | 14.6% | 7 |
| Ashkenazi Jewishnot grpmax-eligible | 14.3% | 7 |
| South Asian | 14.3% | 7 |
| Finnishnot grpmax-eligible | 12.7% | 8 |
| Remaining individualsnot grpmax-eligible | 12.5% | 8 |
| European (non-Finnish) | 10.1% | 10 |
| African / African-American | 9.13% | 11 |
| Amishnot grpmax-eligible | 2.35% | 43 |
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+246del
- MANE Select
- NM_176869
- dbSNP
- rs34420247
- Type
- Deletion
- Location
- chr4:105370591 (GRCh38)
- Gene constraint
- LOEUF 1.324 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.39
Similar variants
- PPA2 p.Gln327fs Uncertain significance ★★ same type
- PPA2 c.442-7del Benign/Likely benign ★★ same type
- PPA2 p.Ala31fs Uncertain significance ★ same type
- PPA2 p.Leu5fs Uncertain significance ★ same type
- PPA2 p.Leu7fs Uncertain significance ★ same type
- PPA2 p.Pro248fs Uncertain significance ★ same type
- PPA2 p.Tyr59del Uncertain significance ★ same type
- PPA2 c.268-15del Benign ★ 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-246del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown