PGAP3 p.Leu307=
c.921G>A · rs761881837 · VCV755096
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0231%, nfe)
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 0.16 | GERP -4.7, phastCons 0.93 |
| Overall | ||
| CADD | 7.597 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0231%
European (non-Finnish) · 273/1,180,010 alleles
Filtering AF
0.0209%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.02%
Overall
0.018%
291/1,614,166 alleles · ultra-rare
exomes 282/1,461,818 · genomes 9/152,348 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0231% | 4,322 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,946 |
| Finnishnot grpmax-eligible | 0.00937% | 10,671 |
| African / African-American | 0.004% | 25,018 |
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
- PGAP3
- Protein
- p.Leu307=
- Coding
- c.921G>A
- MANE Select
- NM_033419
- dbSNP
- rs761881837
- Type
- single nucleotide variant
- Location
- chr17:39672845 (GRCh38)
- Gene constraint
- LOEUF 1.147 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 93.17
Similar variants
- PGAP3 p.Leu307Val Uncertain significance ★★ ⚠ same residue
- PER1 p.Arg307Gln Uncertain significance ★ ⚠ same residue
- PGAP3 c.558-10G>A Pathogenic/Likely pathogenic ★★ same type
- PGAP3 c.694+1G>A Pathogenic ★★ same type
- PGAP3 p.Asp305Gly Pathogenic/Likely pathogenic ★★ same type
- PGAP3 p.Gln89Ter Pathogenic ★★ same type
- PGAP3 p.Glu37Ter Pathogenic ★★ same type
- PGAP3 p.His284Arg Pathogenic/Likely pathogenic ★★ ⚠ 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/pgap3-p-leu307 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown