AGO3 p.Phe859=
c.2577C>T · rs61743816 · VCV786461
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.73%, 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 -0.14 | GERP 1.1, phastCons 0.72 |
| Overall | ||
| CADD | 9.266 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.73%
African / African-American · 2,047/75,008 alleles
Filtering AF
2.63%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.59%
Overall
0.185%
2,991/1,613,792 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.73% | 37 |
| Ashkenazi Jewishnot grpmax-eligible | 0.517% | 193 |
| Middle Eastern | 0.363% | 276 |
| Remaining individualsnot grpmax-eligible | 0.304% | 329 |
| Admixed American | 0.275% | 364 |
| European (non-Finnish) | 0.0334% | 2,994 |
| East Asian | 0.0178% | 5,609 |
| South Asian | 0.0132% | 7,588 |
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
- AGO3
- Protein
- p.Phe859=
- Coding
- c.2577C>T
- MANE Select
- NM_024852
- dbSNP
- rs61743816
- Type
- single nucleotide variant
- Location
- chr1:36055739 (GRCh38)
- Gene constraint
- LOEUF 0.232 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 91.93 · 2 PDB
Similar variants
- AGO3 p.Arg403= Benign/Likely benign ★★ same type
- AGO3 p.Gln781= Benign ★★ same type
- AGO3 p.Glu334= Benign ★★ same type
- AGO3 p.Ala185Thr Uncertain significance ★ ⚠ same type
- AGO3 p.Ala387Gly Uncertain significance ★ ⚠ same type
- AGO3 p.Ala453Ser Uncertain significance ★ same type
- AGO3 p.Ala644Thr Uncertain significance ★ ⚠ same type
- AGO3 p.Ala9Thr 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/ago3-p-phe859 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown