In this study, we introduced a new thermodynamics-based synthesizability descriptor, E min , defined as the excess zero-kelvin energy of a molecule above its lowest energy configurational isomer. Unlike other synthesizability scores, E min is first-principles based with a simple and interpretable meaning. We first found E min to have comparable, if not better, accuracy compared with other well-established synthesizability scores when evaluated on the QM9 dataset. Among molecules with E min = 0, 84% are reported/synthesizable while reported molecules are almost never found above 100 kcal/mol. Next, we augmented other scores with E min , which reduced incorrect "synthesizable" predictions by up to 52%. Our work also explored using E min as a feature for synthesizability ML models, for which it consistently improved accuracy. Accuracy improvements were most pronounced for small training set sizes, making E min suitable for models that have scarce data often associated with novel chemical space. To explore why E min works effectively, we identify common fragments from molecules that E min predicts more correctly than SA Score. Each fragment is paired with a chemical explanation for why E min was able to make correct predictions over SA Score.