PGAP2 p.Pro172=
c.516G>A · rs756891130 · VCV725983
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0329%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.101 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -1.5 | GERP -3.7 |
| Overall | ||
| CADD | 1.37 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0329%
Middle Eastern · 2/6,084 alleles
Filtering AF
0.0058%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00241%
Overall
0.00242%
39/1,614,028 alleles · ultra-rare
exomes 35/1,461,866 · genomes 4/152,162 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0329% | 3,042 |
| European (non-Finnish) | 0.00271% | 36,876 |
| Admixed American | 0.00167% | 60,008 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,488 |
| Finnishnot grpmax-eligible | 0.00156% | 64,008 |
| African / African-American | 0.00133% | 74,914 |
| South Asian | 0.0011% | 91,084 |
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.Pro172=
- Coding
- c.516G>A
- MANE Select
- NM_014489
- dbSNP
- rs756891130
- Type
- single nucleotide variant
- Location
- chr11:3824050 (GRCh38)
- Gene constraint
- LOEUF 0.871 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.00
Similar variants
- PGAP2 p.Pro172Leu Likely benign ★ same residue
- 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
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-pro172 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown