AGO1 p.Ser641=
c.1923C>G · rs148568098 · VCV717672
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.163%, nfe)
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 -0.42 | GERP -1.8, phastCons 0.074 |
| Overall | ||
| CADD | 8.901 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.163%
European (non-Finnish) · 1,921/1,180,022 alleles
Filtering AF
0.157%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.154%
Overall
0.135%
2,171/1,614,104 alleles · rare
exomes 2,052/1,461,886 · genomes 119/152,218 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.163% | 614 |
| South Asian | 0.135% | 741 |
| Remaining individualsnot grpmax-eligible | 0.122% | 822 |
| Admixed American | 0.0467% | 2,143 |
| African / African-American | 0.0227% | 4,413 |
| Finnishnot grpmax-eligible | 0.00937% | 10,669 |
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
- AGO1
- Protein
- p.Ser641=
- Coding
- c.1923C>G
- MANE Select
- NM_012199
- dbSNP
- rs148568098
- Type
- single nucleotide variant
- Location
- chr1:35915437 (GRCh38)
- Gene constraint
- LOEUF 0.164 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 91.45 · 8 PDB
- Residue 641
- the piwi domain; an α-helix
Similar variants
- AGO1 p.Asp356Asn Likely pathogenic ★★ same type
- AGO1 p.Gly199Ser Pathogenic/Likely pathogenic ★★ same type
- AGO1 p.Pro189Leu Likely pathogenic ★★ same type
- AGO1 p.Ala103Val Uncertain significance ★★ ⚠ same type
- AGO1 p.Ala413Val Uncertain significance ★★ ⚠ same type
- AGO1 p.Ala479Val Uncertain significance ★★ ⚠ same type
- AGO1 p.Arg26Gln Uncertain significance ★★ ⚠ same type
- AGO1 p.Arg284His 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/ago1-p-ser641 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown