AGAP1 p.Leu516=
c.1548C>A · rs377419675 · VCV2708215
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0905%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>T here scores Δ0.66 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.053 | GERP 0.43, phastCons 0.89 |
| Overall | ||
| CADD | 11.95 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0905%
East Asian · 39/43,074 alleles
Filtering AF
0.0681%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0602%
Overall
0.00291%
45/1,544,966 alleles · ultra-rare
exomes 42/1,399,372 · genomes 3/145,594 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0905% | 1,104 |
| Remaining individualsnot grpmax-eligible | 0.00835% | 11,979 |
| South Asian | 0.00114% | 87,354 |
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.Leu516=
- Coding
- c.1548C>A
- MANE Select
- NM_001037131
- dbSNP
- rs377419675
- Type
- single nucleotide variant
- Location
- chr2:235968526 (GRCh38)
- Gene constraint
- LOEUF 0.366 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 72.01 · 2 PDB
- Residue 516
- the 'disordered' region; 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-leu516 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown