Is AGO4 p.Val511Met (c.1531G>A) pathogenic?

AGO4 p.Val511Met (c.1531G>A) is classified Uncertain significance in AGO4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-27). AlphaMissense: ambiguous (0.3922); Absent from gnomAD v4.1.

How common is AGO4 p.Val511Met (c.1531G>A) in the general population?

AGO4 p.Val511Met (c.1531G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AGO4 p.Val511Met (c.1531G>A)?

AlphaMissense predicts ambiguous (score 0.3922) — an in-silico prediction, not a clinical call.

AGO4 p.Val511Met

c.1531G>A · rs2523604082 · VCV2313863

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3922 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3922	ambiguous
REVEL	0.1	moderately benign-leaning
SaProt	LLR -10.76	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 0.69, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 22 kb · p 1.1e-24 · regional, not allelic
Overall
CADD	26.9	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

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: AGO4
Protein: p.Val511Met
Coding: c.1531G>A
MANE Select: NM_017629
dbSNP: rs2523604082
Type: single nucleotide variant
Location: chr1:35834141 (GRCh38)
Gene constraint: LOEUF 0.393 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 91.56 · 1 PDB
Residue 511: the piwi domain; a β-strand

Full AGO4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AGO4 p.Val511Ala Uncertain significance ★ ⚠ same residue
AGO4 p.Arg277Trp Uncertain significance ★★ ⚠ same type
AGO4 p.Ala293Pro Uncertain significance ★ ⚠ same type
AGO4 p.Ala449Val Uncertain significance ★ ⚠ same type
AGO4 p.Arg100Gln Uncertain significance ★ ⚠ same type
AGO4 p.Arg100Gly Uncertain significance ★ ⚠ same type
AGO4 p.Arg17Cys Uncertain significance ★ ⚠ same type
AGO4 p.Arg18Cys 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/ago4-p-val511met (accessed [today's date]).

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