Sir Mark Sedwill has announced he will leave his joint roles as cabinet secretary and national security adviser.
In a letter to the prime minister, he said would stand down in September.
Sir Mark will be replaced as national security adviser by David Frost, who is currently leading the Brexit negotiations for the UK.
The civil servant is reported to have had a tense relationship with Boris Johnson’s chief aide Dominic Cummings.
Home secretary Priti Patel said earlier on Sunday it was up to the PM to decide who should occupy the ‘big role’ of cabinet secretary as rumours swirled Sir Mark was to be ousted this week.
The Financial Times and the Sunday Telegraph reported the would step down from his post as the most senior figure in the Civil Service as soon as Monday.
It comes as Downing Street prepares for an overhaul of how the Cabinet Office and Civil Service functions, with Johnson strongly tipped to break up the roles of cabinet secretary and national security adviser – positions united by his predecessor Theresa May.
Patel, asked about the reports predicting Sir Mark’s departure, said: ‘Reform of the Civil Service is a matter that gets discussed in Government and obviously a big role like that is subject to the Prime Minister.’
Speaking to Sky News’ Sophy Ridge On Sunday programme, she added Johnson would need the ‘right kind of support around him’ to deliver on the government’s ‘levelling up’ priorities.
Hinting changes could be afoot, Patel said: ‘The fact of the matter is right now this government is focused on getting on and doing its jobs, delivering for the country, levelling up, focusing on social justice.
‘This is the people’s Government delivering on the people’s priorities and effectively any reforming government will be based around the type of delivery that our Prime Minister wants to drive for our great country and obviously have the right kind of support around him to deliver that.’
Number 10 on Saturday announced a series of reforms which will see Johnson given a firmer grip over his Cabinet.
He will chair a number of new ‘strategic committees’ as part of his Cabinet operation, which government sources said would be ‘responsible for setting direction on the Government’s domestic, international and economic priorities’.
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