PGAP2 p.Phe96Leu
c.286T>C · VCV3931119
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0209%, sas)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.1 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 6.2 | GERP 0.79, phastCons 1 |
| Regional constraint | o/e 0.88 | unconstrained · MANE · 14 kb · p 0.023 · regional, not allelic |
| Overall | ||
| CADD | 22.1 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0209%
South Asian · 19/91,092 alleles
Filtering AF
0.0136%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0114%
Overall
0.00142%
23/1,614,100 alleles · ultra-rare
exomes 22/1,461,878 · genomes 1/152,222 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0209% | 4,794 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,623 |
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.Phe96Leu
- Coding
- c.286T>C
- MANE Select
- NM_014489
- Type
- single nucleotide variant
- Location
- chr11:3817473 (GRCh38)
- Gene constraint
- LOEUF 0.871 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.00
Similar variants
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- 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-phe96leu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown