Is AGO2 p.Val797Met (c.2389G>A) pathogenic?

AGO2 p.Val797Met (c.2389G>A) is classified Likely pathogenic in AGO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-05). AlphaMissense: likely pathogenic (0.9959); Very rare (popmax 0.00167%, amr); Associated with Lessel-Kreienkamp syndrome.

What condition is associated with AGO2 p.Val797Met (c.2389G>A)?

AGO2 p.Val797Met (c.2389G>A) is associated with Lessel-Kreienkamp syndrome (ClinVar).

How common is AGO2 p.Val797Met (c.2389G>A) in the general population?

AGO2 p.Val797Met (c.2389G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about AGO2 p.Val797Met (c.2389G>A)?

AlphaMissense predicts likely pathogenic (score 0.9959) — an in-silico prediction, not a clinical call.

AGO2 p.Val797Met

c.2389G>A · rs1467755029 · VCV1992346

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9959 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Lessel-Kreienkamp syndrome

Computational evidence

Protein change
AlphaMissense	0.9959	likely pathogenic ✓ concordant with ClinVar
REVEL	0.513	indeterminate
SaProt	LLR -14.57	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 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.42	unconstrained · MANE · 25 kb · p 1.2e-55 · regional, not allelic
Overall
CADD	31.0	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 0.00167% Admixed American · 1/60,034 alleles

Overall 0.000205% 3/1,461,878 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,034
African / African-American	0.00133%	75,074
European (non-Finnish)	8.47e-05%	1,180,057

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.Val797Met
Coding: c.2389G>A
MANE Select: NM_012154
dbSNP: rs1467755029
Type: single nucleotide variant
Location: chr8:140532498 (GRCh38)
Gene constraint: LOEUF 0.102 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 92.82 · 71 PDB
Residue 797: the 'interaction with guide rna' region; the piwi domain

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.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
AGO2 p.Gln360His Likely pathogenic ★ 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-val797met (accessed [today's date]).

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