AGAP1 p.Ile680=
c.2040C>T · rs772731242 · VCV2198302
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0329%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.107 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -6.6 | GERP -3.8 |
| Overall | ||
| CADD | 7.049 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0329%
Middle Eastern · 2/6,084 alleles
Filtering AF
0.0101%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00811%
Overall
0.00762%
123/1,614,062 alleles · ultra-rare
exomes 109/1,461,894 · genomes 14/152,168 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0329% | 3,042 |
| South Asian | 0.0165% | 6,073 |
| African / African-American | 0.012% | 8,323 |
| European (non-Finnish) | 0.00754% | 13,259 |
| Admixed American | 0.005% | 19,999 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,829 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,608 |
| East Asian | 0.00223% | 44,888 |
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.Ile680=
- Coding
- c.2040C>T
- MANE Select
- NM_001037131
- dbSNP
- rs772731242
- Type
- single nucleotide variant
- Location
- chr2:236049207 (GRCh38)
- Gene constraint
- LOEUF 0.366 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 72.01 · 2 PDB
- Residue 680
- the arf-gap domain
Similar variants
- AGAP1 p.Ile680Val Uncertain significance ★ ⚠ same residue
- 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
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-ile680 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown