As someone who hires people (I am hiring right now, see bottom of the post), I often get emails asking whether someone should apply for a role I've listed.
If you're considering contacting a hiring manager to ask if you're a good fit for the role, you should just apply.

Why?

• Job descriptions are wish lists.
  Everyone wants someone who checks all the boxes. If the dream candidate applies, you'll probably get rejected. In reality, everyone has weaknesses, and an 80% match candidate is highly competitive.
• Self-skepticism correlates with candidate quality.
  Applicant pools are filled with people who can't do the job but don't understand their abilities well enough to realize it. Conversely, many highly competent professionals self-select out. If you are humble and self-reflective enough to consider your chances honestly, you are probably more competitive than you think.
• You probably won't get a response.
  Hiring is always a busy time, and hiring managers don't have time to review every email. Often, you'll receive nothing, leaving you with wasted effort. I try to reply as much as I can, but there's only so much that can be done.
• Any response you get is biased toward yes.
  If an org has a good filtering process, the biggest determinant in hire quality is whether good candidates apply. More "bad fit" candidates pose little strain, while one more "great fit" candidate could double the success of the hiring round. The incentive is always to get more people to apply.
  It's unclear whether a seeming good fit is a great fit who is overly worried about their weaknesses or a bad fit exaggerating their strengths, but it doesn't matter. Hiring managers are better off if both apply so they encourage them to do so. As a result, you spend some time writing an email, the hiring manager spends some time reviewing your email, they take time to send a response, and you receive the answer that you probably should apply, so all that effort led to nothing. Skipping the email saves you (and me) time in the long run.
• The information transmitted in an email is not always in your favor.
  The fact that someone sent an email can suggest self-reflectiveness (good), but it can also be a sign of a lack of confidence (bad). It can suggest thoughtfulness about time management (good), but it can also signal a lack of agency and autonomy (bad). These signals are very small in magnitude, so I don't, and I hope others don't, read into this too much. However, it's worth realizing what you might be accidentally communicating.

Notable exceptions, where you should email:

• You require something from the job that the description doesn't specify.
  If you need to know whether a job will meet your needs, that's fully worth checking before applying. That's very different from asking a hiring manager to evaluate your fit for the role over email.
• You are fully confident that you do not fit a logistical requirement of the role but you have a creative work around that you want to propose to the organization.
  Hiring is always trying to solve a problem. A good hiring manager will recognize that hiring for the specific role isn't the only solution. If you can solve the problem (e.g. you are unable to work full-time but believe you could still own the key components of the role as a part-time worker), you should consider reaching out.
• You find the job just after the deadline has passed and you need the form re-opened for you.
  Expect a no, but there's very little harm in asking. Note that this is different from if you found the job before the deadline and forgot to apply in time.
• The first stage of the application process is particularly onerous.
  We try to keep our first stage applications at 30 minutes or less, and that's where I'm basing my conclusions. If an application takes multiple hours, you're still likely to receive a yes, but a tiny chance of saving 3 hours of work might be worth a few minutes.

To be clear, the urge to send an email to check if you should apply is totally normal (I have done it before), and anyone who has done this has nothing to worry about. However, I would strongly recommend applying despite your reservations. You can just do things!

Also, if you want to apply to become Access to Medicines Initiative's Head of Monitoring, Evaluation, and Data, JOB DESCRIPTION AND APPLICATION HERE: https://docs.google.com/document/d/1nqOz2a5bTQs5W361G5gpJ3brLEf6xuG0

Unless you have a good reason to believe otherwise, whatever you are doing now is probably not the most impactful thing that you will ever do. Over time, you will have more career capital, which will open more opportunities for impact. If that's true, a large portion of the value of your current project is building career capital for future projects.

As a result, all else equal, we should perhaps be slightly skewed towards tractability in the typical ITN framework. A successful project looks better for career capital than a failed one, even if the two projects were equal from a pure EV comparison.

With that said, most people skew risk-averse, so maybe this is already built in?

EDIT: I agree with @Charlie_Guthmann 's comment that while this may be true, most people already (unintentonally) take this consideration into account due to natural biases, like risk-aversion, MORE than they should.

Thinking back to my first big (well, big for me) donation and an unusual series of thoughts I had. Sharing in case anyone has experienced the same.
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I've practiced frugality to a significant extent, largely because I want to donate/salary sacrifice so much of my income to effective charities. As a result, whenever I'm spending a significant amount of money on anything, alarm bells go off.

I was surprised that alarm bells went off when donating. I had thought through where I donated extensively, and charity was the reason why I wanted to save money in the first place. But I still felt stressed because I was "spending money."

This is such a clear example of missing the forest for the trees. I think we need to be careful about instrumental values/rules and making sure they don't become absolute limitations that decrease overall impact.

AIM just announced that they opened applications to the Charity Entrepreneurship Incubation Program. For those interested, I recently wrote this piece outlining what I did to get accepted to the program. I hope it can be a useful resource for you.

Most importantly, my first tip: APPLY!