---
title: What Is Variant Calling?
description: Learn the fundamentals of variant calling, key workflows, and tools to confidently identify genetic differences in sequencing analysis with SoftGenetics.
---

[Guides for Sequencing, Fragment and Forensics](https://go.softgenetics.com/guides)

# [What Is Variant Calling?](https://go.softgenetics.com/guides/what-is-variant-calling)

 Written by [SoftGenetics Team](https://go.softgenetics.com/guides/author/softgenetics-team) | Aug 13, 2025 2:53:54 PM

## A Guide for New and Experienced Researchers

Variant calling is the process of identifying genetic differences between a sample and a reference genome. It’s a core part of sequencing analysis used in everything from clinical diagnostics and human identification to agriculture.

This guide outlines the basics, common workflows, and tools that streamline variant calling.

## **What Types of Variants Are Detected?**

- SNVs (Single Nucleotide Variants)
- Indels (Insertions and Deletions)
- Structural Variants (e.g., duplications, inversions, translocations)
- Copy Number Variants (CNVs)

## **What Platforms Support Variant Calling?**

- **Sanger Sequencing**: High accuracy; useful for validation as a golden standard
- **NGS (Illumina, and many others of short reads)**: High-throughput, scalable
- **Long-Read (ONT, PacBio)**: Ideal for SVs, phasing, and difficult regions using short reads

## **How Variant Calling Works**

1. **Align reads** to a reference genome
2. **Preprocess data** (e.g., remove duplicates, trim adapters, mask low quality points)
3. **Call variants** using statistical models
4. **Filter and annotate** to give high confidence variants and protein changes
5. **Interpret and validate** with visualization or secondary tools

## **SoftGenetics Solutions**

- - - [**Mutation Surveyor®**](https://www.softgenetics.com/mutationSurveyor.html): Validated variant caller for Sanger Sequences

- - - [**NextGENe®**](https://www.softgenetics.com/NextGENe.html): End-to-end NGS variant calling with annotation and reporting

- - - [**NextGENeLR™**](https://www.softgenetics.com/NextGENeLR.html): Tailored for long-read variant detection

Try our Softgenetics solututions with a free [ 35-day trial](https://www.softgenetics.com/information/request-trial/)

## **Advanced Consideration**

Advanced variant calling workflows — especially in cancer, rare disease, or regulatory contexts — require deeper control and interpretability:

- **Soft-clipped read inspection** in NextGENe enables detection of insertions or SV breakpoints
- Users can filter variants using **multiple quality metrics**, such as:
  
    - **DP (read depth)**
    - **MQ (mapping quality)**
    - **SB (strand bias)**
    - **FS (Fisher’s strand test p-value)**
- Combine **somatic and germline variant filtering** with CNV/LOH analysis for comprehensive tumor profiling
- Generate **locked-down pipelines** with fixed thresholds, automated reporting, and ISO/CLIA documentation compliance
- Support for **ensemble calling**, integrating outputs from GATK, FreeBayes, and VarDict
- **Trio/family analysis**: Identify de novo variants and Mendelian violations
- BAM-level curation and export to genome browsers or VCF annotation pipelines (e.g., Ensembl VEP)

NextGENe and NextGENeLR provide both visual interpretability, easy to use for biologists and compatibility with command-line pipelines — ideal for both clinical labs and advanced research groups.

**Conclusion**

Variant calling is a foundational step in genomics. Whether you’re confirming a clinical variant or exploring structural changes across the genome, SoftGenetics tools offer the control, visibility, and validation support needed to call variants confidently and accurately.

[View full post](https://go.softgenetics.com/guides/what-is-variant-calling)

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