Is AGO2 p.Ile61Val (c.181A>G) pathogenic?

AGO2 p.Ile61Val (c.181A>G) is classified Uncertain significance in AGO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-06). AlphaMissense: likely benign (0.3361); Very rare (popmax 0.00475%, nfe); Associated with Inborn genetic diseases.

What condition is associated with AGO2 p.Ile61Val (c.181A>G)?

AGO2 p.Ile61Val (c.181A>G) is associated with Inborn genetic diseases (ClinVar).

How common is AGO2 p.Ile61Val (c.181A>G) in the general population?

AGO2 p.Ile61Val (c.181A>G) is very rare (popmax 0.00475%, nfe) (gnomAD).

What do computational predictors say about AGO2 p.Ile61Val (c.181A>G)?

AlphaMissense predicts likely benign (score 0.3361) — an in-silico prediction, not a clinical call.

AGO2 p.Ile61Val

c.181A>G · rs779967577 · VCV2333832

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3361 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00475%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3361	likely benign
REVEL	0.148	moderately benign-leaning
SaProt	LLR -10.61	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
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 0.72	unconstrained · MANE · 73 kb · p 6.5e-05 · regional, not allelic
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00475% European (non-Finnish) · 56/1,180,038 alleles

Filtering AF 0.00375% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00337%

Overall 0.00359% 58/1,614,108 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00475%	21,072
Remaining individualsnot grpmax-eligible	0.0016%	62,484
African / African-American	0.00133%	74,942

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.Ile61Val
Coding: c.181A>G
MANE Select: NM_012154
dbSNP: rs779967577
Type: single nucleotide variant
Location: chr8:140585153 (GRCh38)
Gene constraint: LOEUF 0.102 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 92.82 · 71 PDB
Residue 61: a β-strand

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AGO2 p.Cys751Tyr Pathogenic/Likely pathogenic ★★ same condition
AGO2 p.Arg630His Uncertain significance ★★ ⚠ same condition
AGO2 p.Asp89Glu Uncertain significance ★★ ⚠ same condition
AGO2 p.Glu46Lys Uncertain significance ★★ ⚠ same condition
AGO2 p.Pro602Arg Uncertain significance ★★ ⚠ same condition
AGO2 p.Thr158Met Uncertain significance ★★ ⚠ same condition
AGO2 p.Thr444Ala Uncertain significance ★★ ⚠ same condition
AGO2 p.Val154Ile 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-ile61val (accessed [today's date]).

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