AGAP1 p.Ile583=
c.1749C>T · rs781070427 · VCV2177951
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0351%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.82 | GERP -3.5, phastCons 0.004 |
| Overall | ||
| CADD | 11.67 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0351%
South Asian · 32/91,088 alleles
Filtering AF
0.0256%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0222%
Overall
0.00527%
85/1,614,194 alleles · ultra-rare
exomes 76/1,461,892 · genomes 9/152,302 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0351% | 2,846 |
| East Asian | 0.00669% | 14,958 |
| European (non-Finnish) | 0.00398% | 25,107 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,256 |
| Finnishnot grpmax-eligible | 0.00156% | 64,024 |
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
- AGAP1
- Protein
- p.Ile583=
- Coding
- c.1749C>T
- MANE Select
- NM_001037131
- dbSNP
- rs781070427
- Type
- single nucleotide variant
- Location
- chr2:236036664 (GRCh38)
- Gene constraint
- LOEUF 0.366 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 72.01 · 2 PDB
- Residue 583
- the ph domain
Similar variants
- AGAP1 p.Ala418Ser Uncertain significance ★★ ⚠ same type
- AGAP1 p.Ala52Ser Uncertain significance ★★ ⚠ same type
- AGAP1 p.Ala570Gly Uncertain significance ★★ same type
- AGAP1 p.Ala809Ser Uncertain significance ★★ ⚠ same type
- AGAP1 p.Arg14Trp Uncertain significance ★★ ⚠ same type
- AGAP1 p.Arg313His Uncertain significance ★★ ⚠ same type
- AGAP1 p.Arg696Trp Uncertain significance ★★ ⚠ same type
- AGAP1 p.Arg770Cys 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/agap1-p-ile583 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown