High-throughput sequencing (HTS) has revolutionized science by enabling super-fast detection of genomic variants at base-pair resolution. Consequently, it poses the challenging problem of identification of technical artifacts, i.e. hidden non-random error patterns. Understanding the properties of sequencing artifacts holds the key in separating true variants from false positives. Here, we develop Mapinsights, a toolkit that performs quality control (QC) analysis of sequence alignment files, capable of detecting outliers based on sequencing artifacts of HTS data at a deeper resolution compared with existing methods. Mapinsights performs a cluster analysis based on novel and existing QC features derived from the sequence alignment for outlier detection. We applied Mapinsights on community standard open-source datasets and identified various quality issues including technical errors related to sequencing cycles, sequencing chemistry, sequencing libraries and across various orthogonal sequencing platforms. Mapinsights also enables identification of anomalies related to sequencing depth. A logistic regression-based model built on the features of Mapinsights shows high accuracy in detecting 'low-confidence' variant sites. Quantitative estimates and probabilistic arguments provided by Mapinsights can be utilized in identifying errors, bias and outlier samples, and also aid in improving the authenticity of variant calls.