AGAP1 p.Leu666=
c.1996C>T · rs79478544 · VCV2043399
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 1.08%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.091 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 3.4 | GERP 0.53, phastCons 1 |
| Overall | ||
| CADD | 10.06 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.08%
African / African-American · 814/75,050 alleles
Filtering AF
1.02%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.998%
Overall
0.0571%
922/1,614,220 alleles · low-frequency
exomes 457/1,461,888 · genomes 465/152,332 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.08% | 92 |
| Middle Eastern | 0.0825% | 1,212 |
| Remaining individualsnot grpmax-eligible | 0.0816% | 1,226 |
| Admixed American | 0.0416% | 2,401 |
| South Asian | 0.0143% | 7,006 |
| European (non-Finnish) | 0.00119% | 84,289 |
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.Leu666=
- Coding
- c.1996C>T
- MANE Select
- NM_001037131
- dbSNP
- rs79478544
- Type
- single nucleotide variant
- Location
- chr2:236049163 (GRCh38)
- Gene constraint
- LOEUF 0.366 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 72.01 · 2 PDB
- Residue 666
- the arf-gap 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-leu666 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown