Is AGO3 p.Pro524= (c.1572G>A) pathogenic?

AGO3 p.Pro524= (c.1572G>A) is classified Benign in AGO3 (ClinVar, Single submitter, 3 submitters; last evaluated 2019-12-31). Rare (popmax 0.433%, afr).

How common is AGO3 p.Pro524= (c.1572G>A) in the general population?

AGO3 p.Pro524= (c.1572G>A) is rare (popmax 0.433%, afr) (gnomAD).

AGO3 p.Pro524=

c.1572G>A · rs138501451 · VCV780766

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.433%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.9	GERP -4.5
Overall
CADD	7.092	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.433% African / African-American · 325/75,020 alleles

Filtering AF 0.394% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.379%

Overall 0.0681% 1,099/1,612,864 alleles · rare exomes 836/1,460,582 · genomes 263/152,282 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.69%	59
African / African-Americangrpmax	0.433%	231
Remaining individualsnot grpmax-eligible	0.168%	595
Admixed American	0.0918%	1,089
Middle Eastern	0.033%	3,026
European (non-Finnish)	0.00941%	10,624
South Asian	0.0033%	30,291

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: AGO3
Protein: p.Pro524=
Coding: c.1572G>A
MANE Select: NM_024852
dbSNP: rs138501451
Type: single nucleotide variant
Location: chr1:36027279 (GRCh38)
Gene constraint: LOEUF 0.232 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.93 · 2 PDB
Residue 524: the piwi domain

Full AGO3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AGO3 p.Arg403= Benign/Likely benign ★★ same type
AGO3 p.Gln781= Benign ★★ same type
AGO3 p.Glu334= Benign ★★ same type
AGO3 p.Phe859= Benign ★★ same type
AGO3 p.Ala185Thr Uncertain significance ★ ⚠ same type
AGO3 p.Ala387Gly Uncertain significance ★ ⚠ same type
AGO3 p.Ala453Ser Uncertain significance ★ same type
AGO3 p.Ala644Thr 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/ago3-p-pro524 (accessed [today's date]).

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