AGO2 p.His144=
c.432C>T · VCV4820702
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.526%, 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 -1.6 | GERP -3.8 |
| Overall | ||
| CADD | 8.031 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.526%
African / African-American · 395/75,064 alleles
Filtering AF
0.483%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.467%
Overall
0.0406%
655/1,614,114 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.526% | 190 |
| Admixed American | 0.0533% | 1,876 |
| Middle Eastern | 0.0497% | 2,012 |
| Remaining individualsnot grpmax-eligible | 0.0432% | 2,315 |
| East Asian | 0.0267% | 3,740 |
| European (non-Finnish) | 0.0147% | 6,782 |
| South Asian | 0.0132% | 7,590 |
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.His144=
- Coding
- c.432C>T
- MANE Select
- NM_012154
- Type
- single nucleotide variant
- Location
- chr8:140562539 (GRCh38)
- Gene constraint
- LOEUF 0.102 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 92.82 · 71 PDB
- Residue 144
- an α-helix
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-his144 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown