Is AGO2 p.Met78Val (c.232A>G) pathogenic?

AGO2 p.Met78Val (c.232A>G) is classified Uncertain significance in AGO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-22). AlphaMissense: likely pathogenic (0.5703); Very rare (popmax 8.49e-05%, nfe).

How common is AGO2 p.Met78Val (c.232A>G) in the general population?

AGO2 p.Met78Val (c.232A>G) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

What do computational predictors say about AGO2 p.Met78Val (c.232A>G)?

AlphaMissense predicts likely pathogenic (score 0.5703) — an in-silico prediction, not a clinical call.

AGO2 p.Met78Val

c.232A>G · VCV3766228

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5703 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5703	likely pathogenic
REVEL	0.275	benign-leaning
SaProt	LLR -10.55	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 0.79, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 73 kb · p 6.5e-05 · regional, not allelic
Overall
CADD	24.2	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 8.49e-05% European (non-Finnish) · 1/1,178,490 alleles

Overall 6.86e-05% 1/1,456,960 alleles · very rare

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.Met78Val
Coding: c.232A>G
MANE Select: NM_012154
Type: single nucleotide variant
Location: chr8:140572916 (GRCh38)
Gene constraint: LOEUF 0.102 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 92.82 · 71 PDB
Residue 78: an α-helix

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-met78val (accessed [today's date]).

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