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(1) The difference between Tom, Pesopo and Putang is that Tom and Pesopo are boys, while Putang is a girl.

(2) The differences between Tom, Pesopo and Putang are that Tom and Pesopo are manly and unkind, while Putang is unmanly and kind.

Please correct my composition aboveEmotion: big smile
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unmanly is only applied to boys and men (and even then, rarely to boys), so saying that Putang is unmanly is bizarre!

These thoughts would not likely be expressed in the way you've written them, and the problem of between and among would not even occur. There is no need to say things like "The difference is ..." when the sentence itself states the difference.

Tom and Pesopo are boys, while Putang is a girl.
Tom and Pesopo are manly and unkind, while Putang is unmanly (???) and kind.


Nevertheless, your use of difference is and differences are is correct.

CJ

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Thanks CalifJim[A]