PGAP1 c.649+301del
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 2.94%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +301 | deep intronic (+301 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -6.6 | GERP -0.27 |
| Overall | ||
| CADD | 0.015 | PHRED · no single calibrated threshold — expert panels disagree |
| Region caveats | ||
| Repeat context | tandem | AluSx3 sine, simple repeat · ambiguous alignment · confidence, not pathogenicity |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.94%
Middle Eastern · 4/136 alleles
Filtering AF
1.94%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.77%
Overall
1.52%
1,257/82,462 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 2.94% | 34 |
| Amishnot grpmax-eligible | 2.71% | 37 |
| South Asian | 2.41% | 42 |
| Remaining individualsnot grpmax-eligible | 2.04% | 49 |
| European (non-Finnish) | 1.65% | 61 |
| African / African-American | 1.56% | 64 |
| Admixed American | 1.26% | 79 |
| Ashkenazi Jewishnot grpmax-eligible | 1.22% | 82 |
| East Asian | 0.638% | 157 |
| Finnishnot grpmax-eligible | 0.0884% | 1,131 |
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
- Coding
- c.649+301del
- MANE Select
- NM_024989
- dbSNP
- rs531959600
- Type
- Deletion
- Location
- chr2:196912581 (GRCh38)
- Gene constraint
- LOEUF 0.691 · pLI 0.02 (gnomAD)
- Structure
- AlphaFold pLDDT 89.15
Similar variants
- PGAP1 p.Leu681fs Pathogenic/Likely pathogenic ★★ same type
- PGAP1 c.1089+5del Likely pathogenic ★ same type
- PGAP1 c.1426+1del Likely pathogenic ★ same type
- PGAP1 p.Asn223fs Pathogenic ★ same type
- PGAP1 p.Asn7fs Pathogenic ★ same type
- PGAP1 p.Asp192fs Likely pathogenic ★ same type
- PGAP1 p.Cys623fs Pathogenic ★ same type
- PGAP1 p.Lys308fs 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/pgap1-c-649-plus-301del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown