Adult Cystic Fibrosis

The CFTR variant c.2684G>A (leading to p.S895N or p.Ser895Asn) is a rare missense change in the CFTR gene. Available evidence indicates it does not cause classic cystic fibrosis (CF) on its own or even in combination with known CF-causing variants.

Does It Directly Cause Bronchiectasis?

By itself (heterozygous, one copy) — Unlikely to cause bronchiectasis in most cases. Single CFTR variants are common in the general population (carrier rate ~1/25–1/30 for classic CF mutations, though this specific variant is rarer) and typically do not lead to significant lung disease without a second mutation or other risk factors.
In combination (compound heterozygous or with modifiers) — It can contribute to or cause bronchiectasis, as evidenced by the reported case. CFTR-related disorders span a spectrum, from classic cystic fibrosis (severe, with two pathogenic mutations) to milder CFTR-related metabolic syndrome or isolated bronchiectasis.
Bronchiectasis is multifactorial: infections, immune issues, environmental factors, and genetics often interact. Rare CFTR variants like this may predispose individuals to bronchiectasis, especially if paired with another variant or in the presence of other risks.

In summary, p.S895N alone is unlikely to cause bronchiectasis, as it appears to be a mild or benign polymorphism more common in East Asians. However, in combination with other CFTR variants, it may contribute to CFTR-related bronchiectasis in Asian individuals, though CF and related disorders remain rare in Asia compared to Caucasian populations. Genetic counseling and testing for compound variants would be recommended for definitive assessment in at-risk individuals.

helen1000, There is an ongoing discussion of Adult Cystic Fibrosis in the Lung Health forum.

@helen1000
Helen, I had BE for 19 years , then was tested for cf in 2025. They found one variant, so not full blown cf but, according to my pulmonologist, it is the major risk factor for my BE. A sweat test at NJH a few years ago was in the high normal range so they did not do the genetic testing. My pulmonologist (Emory in Atlanta) who ordered it did so based on my CT scan and the patterns he saw in it. They should be able to run full genetic testing to see if you have more variants. Since it’s genetic, I don’t see how you could develop more variants- they’re either there or not. Good luck going forward

HI Cayenne,
Thanks for your tips. My mother had lung cancer in 2018 due to an EGFR mutant. As we age, we may develop more mutant, which is my guess? I would think there is a correlation between the CF mutant and lung disease, though many studies did not see the correlation. I appreciate your feedback!

@ckscoville Great to know! Thank you!

@cayenne Eric Sorscher at Emory is studying the use of Trikafta in BE treatment of NTM infections in CF carriers in a small clinical trial (ID NCT05743946)
Here's a link to a the case reports that led to the trial. They used Trikafta (aka ETI) in 3 people without CF but with BE and NTM infections who all carry F508del, the most common CF mutation in the Caucasian population.
https://www.gavinpublishers.com/article/view/treating-non-cystic-fibrosis-bronchiectasis-with-cftr-modulators-early-case-reports

@tw508
Thank you for that information. I know that Trikafta can be enormously helpful for cf carriers. Unfortunately I couldn’t tolerate the drug.

They are testing another set of CFTR modulators (from Sionna Therapeutics) in an effort to find a treatment for people who aren't eligible for, or cannot tolerate, Vertex modulators. Only in Ph 2 at the moment, but they seem to actually be more effective in normalizing CFTR function than the miraculous Vertex drugs! (Also, some people can tolerate the Vertex drugs at a lower dose, so that might be worth looking into. Alyftrek, the latest generation of Vertex drugs, might be worth a try as well.)