The c.1924T>C variant in SLC26A4 is a missense variant predicted to cause the substitution of serine by proline at amino acid 642 (p.Ser642Pro). The highest population minor allele frequency in gnomAD v2.1.1 is 0.005308 (188/35420 alleles) in Latio/Admixed American population, which is higher than the ClinGen Hearing Loss VCEP threshold (>0.003) for BS1, and therefore meets this criterion (BS1). The computational predictor REVEL gives a score of 0.724, which is above the threshold of 0.7, evidence that correlates with impact to SLC26A4 function (PP3). This variant has been detected in at least one individual with Pendred syndrome who was reported to have a second pathogenic SLC26A4 variant with an unknown phase (0.5 PM3 points, SCV000060117.6.6) (PM3_Supporting). At least one proband with this variant displayed features of sensorineural hearing loss and enlarged vestibular aqueduct, a phenotype specific for Pendred syndrome (PP4, SCV000060117.6.6). In summary, due to conflicting evidence, this variant has been classified as uncertain for autosomal recessive Pendred syndrome based on the ACMG/AMP criteria applied as specified by the ClinGen Hearing Loss VCEP: BS1, PP3, PM3_Supporting, PP4 (ClinGen Hearing Loss VCEP specifications version 2; 10/31/2022).