PGAP2 p.Leu215=
c.645C>G · rs559872012 · VCV3046288
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0134%, eas)
Conditions
1
PGAP2-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.281 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 0.7 | GERP -0.032, phastCons 0.22 |
| Overall | ||
| CADD | 6.819 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0134%
East Asian · 6/44,884 alleles
Filtering AF
0.00579%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00394%
Overall
0.00409%
66/1,614,226 alleles · ultra-rare
exomes 58/1,461,880 · genomes 8/152,346 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0134% | 7,481 |
| European (non-Finnish) | 0.00466% | 21,455 |
| South Asian | 0.00329% | 30,363 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,256 |
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
- PGAP2
- Protein
- p.Leu215=
- Coding
- c.645C>G
- MANE Select
- NM_014489
- dbSNP
- rs559872012
- Type
- single nucleotide variant
- Location
- chr11:3824313 (GRCh38)
- Gene constraint
- LOEUF 0.871 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.00
Disease context
PGAP2-related disorder
Similar variants
- PGAP2 p.Leu215fs Likely pathogenic ★ same residue
- PGAP2 c.349-959A>C Likely benign same condition
- PGAP2 p.Ala127Val Likely pathogenic ★★ same type
- PGAP2 p.Arg238Pro Pathogenic/Likely pathogenic ★★ ⚠ same type
- PGAP2 p.Thr294Met Likely pathogenic ★★ same type
- PGAP2 c.602-3C>T Uncertain significance ★★ same type
- PGAP2 p.Ala187Thr Uncertain significance ★★ ⚠ same type
- PGAP2 p.Ala33Thr 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/pgap2-p-leu215 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown