The idea that Calliope's transness emerges from a disconnect of Cherubic gender and physiology is surface-level. Note that this is the same argument that Calliope uses to deny themself gender in the Epilogues, and they are paired with Roxy's own crossroads of transmasculinity or detransition. While Roxy's paths diverge, and I think the variable nature of the self is an important theme of the Epilogues, Calliope follows them to the same end.

Calliope has a stronger thematic connection to transness than her brother - while Calliope dies shackled to her male counterpart, Caliborn breaks free of those bonds by killing his female half. The game rules that gave Caliborn a straight shot to godhood made the game unwinnable for Calliope. He hits every idea of male power, patriarchy, toxic masculinity that even if his masculinity was elective, he comes to be its definition.

Even before predomination, Calliope is disconnected from and ashamed of her own body. Her clothing is consistently exterior to Caliborn's shirt and suspenders, and dressing up as her trollsona is one of her few comforts in solitude. When she meets her friends in the void, she worries that not wearing her troll costume would make her too scary.

So what does this mean to Roxy, who struggles to fill the role of mother? It means that Calliope has managed to reclaim for herself womanhood, what Roxy could only handle with obsession and addiction. Using the narrative framework that Calliope herself provided, Roxy's need to attune to a powerful source of Space is thus using Calliope's feminine aspect as a beacon for Roxy to restructure her connection to motherhood towards strength. Roxy and Kanaya are both laden with miscarriage motifs (the funeral for Jaspers; the mutant cats and the Matriorb), and Calliope is the one who gives them the key to surmount those reproductive woes.

That whole sequence of inter-species Lalondian solidarity is just rich in queer joy. There is already great triumph of love over heteronormativity, but a girl hiding from the eidolon of masculinity, one that stole her own skin and blood, finally given a body of her own? That her incarnation lifts the reproductive burdens of entire species from the shoulders of other girls is no surprise; many of the fiercest allies of trans women are among those assigned female but disillusioned within womanhood.