Quasiregular orthographies such as English contain substantial ambiguities between orthography and phonology that force developing readers to acquire flexibility during decoding of unfamiliar words, a skill referred to as a "set for variability" (SfV). The ease with which a child can disambiguate the mismatch between the decoded form of a word and its actual lexical phonological form has been operationalized using the SfV mispronunciation task (e.g., the word "wasp" is pronounced to rhyme with "clasp" [i.e., /waesp/] and the child must recognize the actual pronunciation of the word to be /w[open back rounded vowel]sp/). SfV has been shown to be a significant predictor of word reading variance. However, little is known about the relative strength of SfV as a predictor of word reading compared to other well-established predictors or the strength of this relationship in children with dyslexia. To address these questions, we administered the SfV task to a sample of grade 2-5 children (N = 489) along with other reading related measures. SfV accounted for 15% unique variance in word reading above and beyond other predictors, whereas phonological awareness (PA) accounted for only 1%. Dominance analysis indicated SfV is the most powerful predictor, demonstrating complete statistical dominance over other variables including PA. Quantile regression revealed SfV is a stronger predictor at lower levels of reading skill, indicating it may be an important predictor in students with dyslexia. Results suggest that SfV is a powerful and potentially highly sensitive predictor of early reading difficulties and, therefore, may be important for early identification and treatment of dyslexia.