Is AGO2 p.Asp605Tyr (c.1813G>T) pathogenic?

AGO2 p.Asp605Tyr (c.1813G>T) is classified Uncertain significance in AGO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-16). AlphaMissense: likely pathogenic (0.9868); Absent from gnomAD v4.1.

How common is AGO2 p.Asp605Tyr (c.1813G>T) in the general population?

AGO2 p.Asp605Tyr (c.1813G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AGO2 p.Asp605Tyr (c.1813G>T)?

AlphaMissense predicts likely pathogenic (score 0.9868) — an in-silico prediction, not a clinical call.

AGO2 p.Asp605Tyr

c.1813G>T · VCV3911156

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9868 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9868	likely pathogenic
REVEL	0.547	indeterminate
SaProt	LLR -17.09	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.42	unconstrained · MANE · 25 kb · p 1.2e-55 · regional, not allelic
Overall
CADD	25.0	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.Asp605Tyr
Coding: c.1813G>T
MANE Select: NM_012154
Type: single nucleotide variant
Location: chr8:140544239 (GRCh38)
Gene constraint: LOEUF 0.102 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 92.82 · 71 PDB
Residue 605: a turn; the piwi domain

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-asp605tyr (accessed [today's date]).

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