I agree a lot with Kayke! It's such a hard thing to quantify; I'm not sure there's such a moment for me. I suppose it could be yet to come!
One of my friends once made the comment, "I don't think we ever realised just how popular Today Nothing Happened was." It never felt popular. Yet I got recognised by a stranger while shopping once, and my brother has been recognised twice at work as a "character" from that autobio comic. When I sell more books than I expected it doesn't feel like "wow I must have a big following!" -- it feels more like "wow I'm doing really well for a small comic!"
Things increment so slowly -- there's often not a sudden influx of comments or a moment where you're suddenly getting more. It's more like you get 2 comments on one page, 1 on the next, 2 on the next, then 4, then 2, then 6, then 5, then 3, then 7, then 4, then 6, then 8, then 6, then 6, then 9, then 12, then 8, then 4 -- and you never noticed that somehow 4 comments went from "the most comments I've ever gotten" to "kind of a slow day today."
I guess opening my patreon was the biggest influx of support I was able to tangibly see, since I started mine pretty late in the game, and the support I got was a big surprise. But, does that mean I have a pretty large amount of readers, or a small amount who are disproportionately generous?
So yeah, I'm not, really sure? It feels like there must be a point where the realisation is unavoidable -- where you can't realistically answer all comments, or you're making enough to reliably live on -- but you can have a good-sized audience well before reaching that point. I feel like my current comic does have a significant readership, but if you asked me if it's "large" I'm not sure I could give you a straight answer because I'm just not sure how to quantify that.