The departure of the University of Surrey, the University of Bath and the University of St Andrews from the 1994 Group could herald a further break-up of mission groups as other institutions question their strategic alliances.
The prediction has been made by Julian Beer, pro vice-chancellor for regional enterprise at the University of Plymouth, who is leading a sector-wide study on university strategy.
Professor Beer said other members of the 1994 Group, which represents smaller research-intensive universities, may also be "looking at whether they are still aligned" after the loss of six leading universities this year.
Surrey's decision to leave, announced on 6 November, comes after the appointment of its vice-chancellor Sir Chris Snowden as the next president of Universities UK, which would have been a feather in the cap of the 1994 Group.
Dame Glynis Breakwell, Bath's vice-chancellor, announced last week that the institution was leaving the 1994 Group because "membership ... does not reflect the type of university we are", while St Andrews has confirmed that it left the group last month.
In a statement, a spokesman said that St Andrews was "reviewing our medium- to long-term strategic plans", adding that it had "ranked consistently among the United Kingdom's top 10 universities" in "all national league tables over the past decade".
With the universities of Durham, Exeter, York and Queen Mary, University of London having left to join the Russell Group over the summer, the 1994 Group has just 12 remaining members.
"The 1994 Group have some real issues to address and need to reposition themselves," said Professor Beer.
"They are going to have to widen their entry criteria and look further afield for new members, perhaps beyond just small, research-intensive universities," he said.
However, "micro-fractures" were appearing in all mission groups as universities re-examined their selling points and objectives in the new era of ?9,000 tuition fees, he said.
About a quarter of universities - 34 in total - have updated their mission statements in the past two years, with seven signalling significant changes of direction, he said.
The University of Southampton, he said, had moved away from emphasising its all-round credentials in favour of "research and enterprise". Other research-intensive universities might follow suit, he predicted.
The University of Buckingham and Aston University were leaning towards the professions, while Birmingham City University was now focused on "practice-based education" rather than enterprise.
"A lot of universities are stepping back and thinking [about] where they are and whether they...want to do their own thing," said Professor Beer.
"However, if you can partner with like-minded institutions with similar strengths, that is quite powerful, particularly with research funders. Unless you are Oxford or Cambridge, you don't want to be out on your own as it is harder to seize opportunities as government policy changes."
But, Professor Beer added, greater differentiation makes it harder to hold a mission group together: "Your lobbying is less effective as your message is less clear."
The gap between the Russell Group's five most research-intensive universities and the rest also raised questions about the group's future cohesion, believes Sir David Watson, professor of higher education at the University of Oxford.
He cited past figures showing that the London School of Economics, Imperial College London, University College London, the University of Oxford and the University of Cambridge all gained at least 60 per cent of their Higher Education Funding Council for England income from research, whereas some Russell Group members received only about 30 per cent.
The Russell Group's "tail is increasingly disengaged from its head", said Professor Watson. "Empirically they don't stand up as clusters of institutions with similar profiles and performance."
The turmoil within the 1994 Group follows concerns about its future direction, with plans under discussion to brand its members "student experience universities" rather than focusing on their research strengths.
Disagreement with Bath about the group's direction under its new executive director, Alex Bols, who was appointed in June, is thought to have led to the university's exit.
David Palfreyman, director of the Oxford Centre for Higher Education Policy Studies, argued that it was time for 1994 Group universities to reinvent themselves as elite, teaching-focused institutions. "You could colonise a niche area, particularly if fee bands widen and universities can charge more," he said.
"You would say to students: 'If you go to a Russell Group university, you will be neglected because professors are off doing research.' But these universities could say: 'Come to us and you are in a sweet spot and a place committed to undergraduate teaching.'
"It is difficult...because you are basically giving up on research, but you are segmenting yourself from those pure employability universities.
"You would have to be a brave vice-chancellor to articulate this. It would involve...facing reality rather than just saying, 'We do OK because we get a few crumbs of research.'"