AGO3 p.Pro591=
c.1773A>G · rs139849193 · VCV2638660
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.231%, mid)
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 1.5 | GERP -0.18, phastCons 1 |
| Overall | ||
| CADD | 14.11 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.231%
Middle Eastern · 14/6,062 alleles
Filtering AF
0.14%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.112%
Overall
0.0151%
244/1,614,182 alleles · rare
exomes 207/1,461,842 · genomes 37/152,340 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.231% | 433 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0608% | 1,645 |
| Remaining individualsnot grpmax-eligible | 0.0288% | 3,473 |
| Admixed American | 0.015% | 6,670 |
| European (non-Finnish) | 0.0141% | 7,108 |
| South Asian | 0.0132% | 7,590 |
| African / African-American | 0.00933% | 10,724 |
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.Pro591=
- Coding
- c.1773A>G
- MANE Select
- NM_024852
- dbSNP
- rs139849193
- Type
- single nucleotide variant
- Location
- chr1:36036198 (GRCh38)
- Gene constraint
- LOEUF 0.232 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 91.93 · 2 PDB
- Residue 591
- the piwi domain
Similar variants
- AGO3 p.Arg403= Benign/Likely benign ★★ same type
- AGO3 p.Gln781= Benign ★★ same type
- AGO3 p.Glu334= Benign ★★ same type
- AGO3 p.Phe859= 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
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-pro591 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown