PGAP2 p.Leu69Ser
c.206T>C · VCV3305935
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.135 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 4.3 | GERP 1.9, phastCons 1 |
| Regional constraint | o/e 0.88 | unconstrained · MANE · 14 kb · p 0.023 · regional, not allelic |
| Overall | ||
| CADD | 22.8 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,072 alleles
Filtering AF
0.000878%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000718%
Overall
0.00112%
18/1,613,158 alleles · ultra-rare
exomes 16/1,461,050 · genomes 2/152,108 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,072 |
| European (non-Finnish) | 0.00144% | 69,364 |
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.Leu69Ser
- Coding
- c.206T>C
- MANE Select
- NM_014489
- Type
- single nucleotide variant
- Location
- chr11:3817393 (GRCh38)
- Gene constraint
- LOEUF 0.871 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.00
Similar variants
- PGAP2 p.Ala187Thr Uncertain significance ★★ ⚠ same condition
- PGAP2 p.Ala33Thr Uncertain significance ★★ ⚠ same condition
- PGAP2 p.Arg238Cys Uncertain significance ★★ ⚠ same condition
- PGAP2 p.Glu204Lys Uncertain significance ★★ ⚠ same condition
- PGAP2 p.Leu161Phe Uncertain significance ★★ ⚠ same condition
- PGAP2 p.Val183Met Uncertain significance ★★ ⚠ same condition
- PGAP2 p.Val4Ile Uncertain significance ★★ ⚠ same condition
- PGAP2 p.Val182Ile Benign/Likely benign ★★ same condition
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-leu69ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown