Is AGO2 p.Gln360Pro (c.1079A>C) pathogenic?

AGO2 p.Gln360Pro (c.1079A>C) is classified Uncertain significance in AGO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-23). AlphaMissense: likely pathogenic (0.999); Absent from gnomAD v4.1; Associated with Lessel-Kreienkamp syndrome.

What condition is associated with AGO2 p.Gln360Pro (c.1079A>C)?

AGO2 p.Gln360Pro (c.1079A>C) is associated with Lessel-Kreienkamp syndrome (ClinVar).

How common is AGO2 p.Gln360Pro (c.1079A>C) in the general population?

AGO2 p.Gln360Pro (c.1079A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AGO2 p.Gln360Pro (c.1079A>C)?

AlphaMissense predicts likely pathogenic (score 0.999) — an in-silico prediction, not a clinical call.

AGO2 p.Gln360Pro

c.1079A>C · VCV4077856

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Lessel-Kreienkamp syndrome

Computational evidence

Protein change
AlphaMissense	0.999	likely pathogenic · top 8% in AGO2
REVEL	0.675	pathogenic-leaning
SaProt	LLR -11.77	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
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 0.42	unconstrained · MANE · 25 kb · p 1.2e-55 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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.Gln360Pro
Coding: c.1079A>C
MANE Select: NM_012154
Type: single nucleotide variant
Location: chr8:140556234 (GRCh38)
Gene constraint: LOEUF 0.102 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 92.82 · 71 PDB
Residue 360: an α-helix

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

Disease context

Lessel-Kreienkamp syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AGO2 p.Gln360His Likely pathogenic ★ same residue
AGO2 p.Cys751Tyr Pathogenic/Likely pathogenic ★★ same condition
AGO2 p.Gly201Val Pathogenic/Likely pathogenic ★★ same condition
AGO2 p.Gly604Arg Pathogenic/Likely pathogenic ★★ same condition
AGO2 p.Thr357Met Pathogenic/Likely pathogenic ★★ same condition
AGO2 p.Arg630His Uncertain significance ★★ ⚠ same condition
AGO2 p.Asp89Glu Uncertain significance ★★ ⚠ same condition
AGO2 p.Pro602Arg Uncertain significance ★★ ⚠ same condition

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-gln360pro (accessed [today's date]).

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