The scholars had met inside a wedding hall to celebrate Prophet Mohammed’s birthday, interior ministry spokesman Najib Danish said.
The total of 50 dead and 80 wounded is reported by the Reuters news agency, quoting three government sources, while other reports put the death toll at 43.
The targeted building was the Uranus wedding hall, a massive complex housing several large banqueting halls near the city’s airport.
Kabul police spokesman Basir Mujahid said: “Hundreds of Islamic scholars and their followers had gathered to recite verses from the holy Quran to observe the Eid Milad-un-Nabi festival at the private banquet hall.”
More than 40 people were critically wounded, officials at Kabul’s Emergency Hospital said, confirming that 30 ambulances had rushed to the scene.
The explosion happened at about 6.15pm local time on the airport road in Kabul city centre, local site Tolo News reported.
A witness outside Kabul’s Emergency Hospital told the site “there were a lot of wounded people, I saw at least ten wounded people brought here.”
The attack is the first of its kind against a Sunni religious gathering in Afghanistan, the Washington Post reported.
No one has claimed to have been behind the blast, but both Taliban and Islamic State (IS) groups have targeted religious scholars tied to the government in the past.
IS claimed it carried out a similar attack in June, killing at least seven people and wounding 20 at a meeting of the Afghan Ulema Council, also in the capital.
Made up of the country’s top clerics, the council had issued a decree against suicide attacks and called for peace talks.
On Monday, a three-day meeting between the Taliban and the US special envoy for Afghanistan aimed at establishing a basis for talks ended with no agreement, the militant group said.