PGAP1 p.Leu650=
c.1948T>C · rs1488181217 · VCV436290
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00716%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.4 | GERP 1.3, phastCons 0.83 |
| Overall | ||
| CADD | 8.062 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00716%
South Asian · 6/83,772 alleles
Filtering AF
0.00307%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00209%
Overall
0.000381%
6/1,574,626 alleles · very rare
exomes 6/1,422,462 · genomes 0/152,164 · joint denominator
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
- PGAP1
- Protein
- p.Leu650=
- Coding
- c.1948T>C
- MANE Select
- NM_024989
- dbSNP
- rs1488181217
- Type
- single nucleotide variant
- Location
- chr2:196847951 (GRCh38)
- Gene constraint
- LOEUF 0.691 · pLI 0.02 (gnomAD)
- Structure
- AlphaFold pLDDT 89.15
Similar variants
- PGAP1 p.Leu650Met Uncertain significance ★ ⚠ same residue
- PGAP1 p.Leu650Phe Uncertain significance ★ ⚠ same residue
- PGAP1 p.Arg231Ter Pathogenic/Likely pathogenic ★★ same type
- PGAP1 p.Gln466Ter Pathogenic ★★ same type
- PGAP1 p.Gln555Ter Pathogenic/Likely pathogenic ★★ same type
- PGAP1 p.Tyr758Ter Pathogenic/Likely pathogenic ★★ same type
- PGAP1 p.Ala298Thr Uncertain significance ★★ ⚠ same type
- PGAP1 p.Ala714Val 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/pgap1-p-leu650 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown