Is AGO2 p.Gln274Arg (c.821A>G) pathogenic?

AGO2 p.Gln274Arg (c.821A>G) is classified Uncertain significance in AGO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-15). AlphaMissense: likely benign (0.3246); Absent from gnomAD v4.1.

How common is AGO2 p.Gln274Arg (c.821A>G) in the general population?

AGO2 p.Gln274Arg (c.821A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AGO2 p.Gln274Arg (c.821A>G)?

AlphaMissense predicts likely benign (score 0.3246) — an in-silico prediction, not a clinical call.

AGO2 p.Gln274Arg

c.821A>G · rs2549625583 · VCV1804396

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3246 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3246	likely benign
REVEL	0.242	benign-leaning
SaProt	LLR -9.79	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.20	constrained · MANE · 1,924 bp · p 2.5e-16 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AGO2
Protein: p.Gln274Arg
Coding: c.821A>G
MANE Select: NM_012154
dbSNP: rs2549625583
Type: single nucleotide variant
Location: chr8:140558542 (GRCh38)
Gene constraint: LOEUF 0.102 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 92.82 · 71 PDB
Residue 274: the paz domain; a β-strand

Full AGO2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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-gln274arg (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown