The practices are at risk because most of their partners are over the age of 60 and are likely to seek retirement soon, according to the Royal College of GPs.
The college estimates that 543 practices are at risk - but it could rise to 600.
The extent of the threat is to be revealed today by college chair at the opening of its annual conference in Liverpool.
She warned that by 2022 a thousand GPs a year would be leaving the profession - and 22% of doctors in London could retire within five years.
Last year some 7.9% of GP posts were vacant - nearly four times as many as in 2010.
National targets have been set to recruit 50% of medical graduates to general practice - but in reality just 40% have chosen this course, according to the college.
Comparing general practice to a dam, she said: "So far much of the damage to the dam wall has been hidden from the public - they see the flooding downstream in accident and emergency departments and in hospital pressures, but they haven’t been aware that GPs, nurses and practice teams have been absorbing that pressure by trying to do more and more with less and less.
"But if we let that situation continue we will see whole chunks of the dam fall apart when practices have to shut their doors."
Drugs have been developed to tackle a protein called VEGF - vascular endothelial growth factor.
But cancer researchers in Nottingham, UK, have now discovered a form of VEGF that can prevent pain.
The research has shown that one form of VEGF triggers the growth of blood vessels and can cause pain. But another form stops the growth of blood vessels and controls pain.
Researchers Dr Lucy Donaldson and Dr David Bates are now set to publish their findings in the journal Neurobiology of Disease.
A university spokeswoman said: "The study has centred on understanding how these two types of VEGF work and why the body makes one form rather than the other.
"The academics have been able to switch from the pain stimulating form to the pain inhibiting VEGF in animal models in the laboratory and are now investigating compounds to replicate this in humans. It is thought these compounds could form the basis for new drugs to be tested in humans in clinical trials."
Regulation of alternative VEGF-A mRNA splicing is a therapeutic target for analgesia Neurobiology of Disease November 2014; doi: 10.1016/j.nbd.2014.08.012
Known as ambulatory emergency care, it involves doctors assessing, diagnosing and treating patients on the same day.
Today the Royal College of Physicians publishes a "toolkit" setting out the steps and procedures doctors need to use for the technique.
The college says it is particularly useful for frail, elderly patients who may be better off recovering at home.
Its advice includes four questions to be asked to identify whether this kind of care can be used for a patient arriving at hospital as an emergency.
Developer Dr Vincent Connolly, of South Tees Hospitals NHS Foundation Trust, said it was a "social movement" transforming emergency care.
He said: "Ambulatory Emergency Care is a new paradigm in emergency care, it enables clinical teams to focus on providing care for patients without the need for formal admission to a bed."
Dr Frank Joseph, acute care fellow at the college, said: "The challenges faced by acute services require change to provide new ways of caring for the acutely unwell. Recognition that traditional services and ways of delivering care are not entirely fit for purpose and are unsustainable has led to innovation that seeks to deliver quality, patient centred acute care of which ambulatory emergency care is a prime example."
The guidance says that clinicians should use a 12-lead electrocardiogram during initial assessment of the patient.
It calls on doctors to take a detailed history of patients who suffer blackouts - including the interviewing of witnesses to fainting episodes.
And it sets out "red flags" which should mean urgent referral to a specialist team for assessment of heart disease risks. These include breathlessness, fainting during exertion and a history of heart disorder - and should mean the patient is seen within 24 hours.
The guidance is being published by the National Institute for Health and Care Excellence.
Nick Baillie, from NICE, said: "People often do not feel they need to seek help if they have fainted or had a blackout especially if they feel fine afterwards.
"However blackouts can be the sign of a more serious underlying condition, such as a heart disorder.
"This new quality standard sets out how healthcare professionals should assess any person who is suspected of having a transient loss of consciousness and which tests to use to correctly assess their condition and offer appropriate treatment.”