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"significant shortcoming" is correct and usable in written English.
You can use it when referring to something that has a large, important disadvantage. For example, "The significant shortcoming of this plan is that it doesn't take into account the rising cost of materials."
Exact(40)
But Ms. McCarron acknowledged that soft-shell lobster has a significant shortcoming, aside from its relatively short harvesting season.
"Our inability to seize the initiative in the 'War of Ideas' with Al Qaeda is perhaps our most significant shortcoming so far in the war against terrorism," said the document, dated Sept. 17, 2003.
Throughout the four-week-old trial of John A. Muhammad, the man accused of masterminding the Washington-area sniper attacks, prosecutors have had to work around what seemed a significant shortcoming in their case: most of the evidence linked only Lee Malvo, who is accused of being Mr. Muhammad's accomplice, to the killings.
This is a very significant shortcoming especially in practical time integration.
A significant shortcoming of all these models is that they only regard a deterministic lead time.
Similarly, what is readily observed in implementation of an HMM is the use of various probability tables, and a significant shortcoming is revealed.
Similar(20)
Even so, significant shortcomings remain.
The study had two significant shortcomings.
It worked but had several significant shortcomings.
"All approaches have significant shortcomings," she said, referring to laws in other states.
In reply, the government said the report had significant shortcomings and glossed over recent institutional and legal measures.
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Since I tried Ludwig back in 2017, I have been constantly using it in both editing and translation. Ever since, I suggest it to my translators at ProSciEditing.

Justyna Jupowicz-Kozak
CEO of Professional Science Editing for Scientists @ prosciediting.com