AGO2 p.Val569=
c.1707C>G · rs57810503 · VCV786126
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.61%, afr)
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 1.4 | GERP -1.5, phastCons 1 |
| Overall | ||
| CADD | 6.656 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.61%
African / African-American · 2,708/75,058 alleles
Filtering AF
3.49%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.45%
Overall
0.191%
3,089/1,614,170 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.61% | 28 |
| Admixed American | 0.265% | 378 |
| Remaining individualsnot grpmax-eligible | 0.237% | 422 |
| Middle Eastern | 0.132% | 758 |
| South Asian | 0.00549% | 18,217 |
| European (non-Finnish) | 0.00517% | 19,344 |
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
- AGO2
- Protein
- p.Val569=
- Coding
- c.1707C>G
- MANE Select
- NM_012154
- dbSNP
- rs57810503
- Type
- single nucleotide variant
- Location
- chr8:140547509 (GRCh38)
- Gene constraint
- LOEUF 0.102 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 92.82 · 71 PDB
- Residue 569
- an α-helix; the piwi domain
Similar variants
- AGO2 p.Arg714Trp Pathogenic/Likely pathogenic ★★ same type
- AGO2 p.Cys751Tyr Pathogenic/Likely pathogenic ★★ same type
- AGO2 p.Gly201Val Pathogenic/Likely pathogenic ★★ same type
- AGO2 p.Gly604Arg Pathogenic/Likely pathogenic ★★ same type
- AGO2 p.Thr357Met Pathogenic/Likely pathogenic ★★ same type
- AGO2 p.Ala142Thr Uncertain significance ★★ ⚠ same type
- AGO2 p.Ala372Val Uncertain significance ★★ ⚠ same type
- AGO2 p.Arg630His 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/ago2-p-val569 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown