PGAP2 p.Leu186=
c.558C>T · rs776879191 · VCV3020235
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.205 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -4.2 | GERP -3.7 |
| Overall | ||
| CADD | 1.015 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,084 alleles
Filtering AF
0.00172%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00149%
Overall
0.00223%
36/1,614,066 alleles · ultra-rare
exomes 31/1,461,870 · genomes 5/152,196 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,084 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,241 |
| African / African-American | 0.00267% | 37,468 |
| European (non-Finnish) | 0.00246% | 40,691 |
| Admixed American | 0.00167% | 60,004 |
| South Asian | 0.0011% | 91,090 |
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.Leu186=
- Coding
- c.558C>T
- MANE Select
- NM_014489
- dbSNP
- rs776879191
- Type
- single nucleotide variant
- Location
- chr11:3824092 (GRCh38)
- Gene constraint
- LOEUF 0.871 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.00
Similar variants
- 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
- PGAP2 p.Arg238Cys Uncertain significance ★★ ⚠ same type
- PGAP2 p.Asn205Lys 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-leu186 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown