PGAP2 p.Leu43=
c.129C>A · rs150486631 · VCV750027
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0917%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.065 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 2.2 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 10.44 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0917%
Admixed American · 55/59,994 alleles
Filtering AF
0.0722%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0653%
Overall
0.0144%
233/1,613,926 alleles · ultra-rare
exomes 183/1,461,752 · genomes 50/152,174 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0917% | 1,091 |
| European (non-Finnish) | 0.0146% | 6,860 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,414 |
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.Leu43=
- Coding
- c.129C>A
- MANE Select
- NM_014489
- dbSNP
- rs150486631
- Type
- single nucleotide variant
- Location
- chr11:3811388 (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-leu43 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown