TolerancePaint
It is easy to think a protein is a house of cards — that any letter you change breaks it. AlphaMissense says otherwise: it scores every possible single-letter change in a protein, and most come out harmless. The damaging ones cluster at a minority of critical spots. Paint which stretches you think tolerate change, then reveal the real heatmap and see how much of the protein is actually forgiving. Everything runs locally; nothing about you is collected.
This is the tool. Your painting is scored against the live AlphaMissense predictions for each protein, fetched in your browser from the AlphaFold Database. The proteins are listed below (works without JavaScript).
Loading the game… If it does not start, the full protein guide below still works.
How to play. Press Start. Select a region (slider bar: click, or ←/→) and mark it 1 Tolerant, 2 Mixed, or 3 Sensitive; A paints the whole chain tolerant. Press R to reveal the real AlphaMissense heatmap and score. Press Enter or Next to continue.
What AlphaMissense says
AlphaMissense (Cheng et al., Science 2023) predicts, for every one of the ~19 possible substitutions at every position, whether it is likely benign (pathogenicity ≤ 0.34), likely pathogenic (≥ 0.564), or ambiguous (in between). Laid out as a grid — 20 rows of amino acids by the length of the protein — it is mostly green: across the human proteome roughly a majority of substitutions are predicted benign. The damaging red stripes fall on the buried core, the active site, and key interface residues. That is the whole point of this game (misconception M08): a protein is not a house of cards.
The proteins
| Protein | Gene | Accession | What the heatmap shows |
|---|---|---|---|
| Haemoglobin, beta chain | HBB | P68871 | Mostly tolerant; the sickle-cell change is a single surface substitution (Glu→Val at UniProt position 7, the classic “β6”). |
| PTEN (tumour suppressor) | PTEN | P60484 | A large sensitive fraction — the active site and folded core disable easily; surface loops tolerate change. |
| p53 (tumour suppressor) | TP53 | P04637 | Disordered ends tolerate almost anything; the DNA-binding core (hotspots ~175/248/273/282) does not. |
Methods & about
The heatmap is the live AlphaMissense prediction for each protein, fetched in your
browser from the AlphaFold Database (…-aa-substitutions.csv) and drawn as a grid; your
painting is scored region-by-region against the mean predicted pathogenicity. AlphaMissense is a
prediction, not a clinical verdict — it is a research tool, and a “benign” score is
not medical advice. It predicts a variant’s likely effect on the protein; that is not the
same as clinical pathogenicity (a damaging change can still be tolerated in the body — e.g. through
gene redundancy). The class thresholds (≤ 0.34 benign, ≥ 0.564 pathogenic) are AlphaMissense’s own.
Every protein note is written by hand, not generated, and science-checked. No accounts, no storage, no
servers of ours (your browser talks straight to the AlphaFold Database).
Want to explore variants on a structure? Open the free AlphaFold viewer. Everything we make is free and non-profit; learn more on the home page.