The normal PI phenotype is PI*MM.

More than 95% of people with severe alpha-1 antitrypsin deficiency and emphysema are homozygous for the Z allele (PI*ZZ) and have alpha-1 antitrypsin levels of about 30 to 40 mg/dL (5 to 6 micromol/L). Prevalence in the general population is 1/1500 to 1/5000. Most are whites of Northern European descent; the Z allele is rare in people of Asian descent and blacks. Though emphysema is common among PI*ZZ patients, many nonsmoking patients who are homozygous for PI*ZZ do not develop emphysema; patients who do typically have a family history of COPD. PI*ZZ smokers have a lower life expectancy than PI*ZZ nonsmokers, who have a lower life expectancy than PI*MM nonsmokers and smokers. If they smoke, people who are PI*MZ heterozygous are more likely to experience more rapid decreases in forced expiratory volume in 1 second (FEV1) over time than do people in the general population.

Other rare phenotypes include PI*SZ and two types with nonexpressing alleles, PI*Z-null and PI*null-null (see table Expression of Phenotype in Alpha-1 Antitrypsin Deficiency). The null phenotype leads to undetectable serum levels of alpha-1 antitrypsin. Normal serum levels of malfunctioning alpha-1 antitrypsin may occur with rare mutations.