> For the complete documentation index, see [llms.txt](https://help.connected.illumina.com/llms.txt). Markdown versions of documentation pages are available by appending `.md` to page URLs; this page is available as [Markdown](https://help.connected.illumina.com/dragen/dragen-v4.5/product-guides/dragen-v4.5/germline/small_variants_accuracy.md).
# Small Variants
Generated on **2026-05-07**
## Small variants
The DRAGEN Germline Small Variant Caller takes mapped and aligned DNA reads as input and calls SNPs and indels through a combination of column-wise detection and local de novo assembly of haplotypes. For more information, refer to the [DRAGEN user guide](/dragen/dragen-v4.5/product-guides/dragen-v4.5/dragen-dna-pipeline/small-variant-calling.md).
**DRAGEN**: DRAGEN 4.4.6 vs 4.5.4 | **Truthset**: GIAB/NIST high-confidence, GIAB/NIST v4.2.1 | **Reference**: GRCh38
Results reported for HG001-HG007 sequenced with NSX 1.3 with 10B flow cell downsampled at 35x raw coverage.
SNPs table (click to expand)
| Sample | Version | Recall | Precision | F1-score | FN | FP |
| ------ | ------- | ------ | --------- | -------- | ---- | ---- |
| HG001 | 4.4.6 | 1.000 | 0.999 | 0.999 | 1336 | 2634 |
| HG001 | 4.5.4 | 1.000 | 1.000 | 1.000 | 721 | 1658 |
| HG002 | 4.4.6 | 0.999 | 1.000 | 0.999 | 2896 | 1749 |
| HG002 | 4.5.4 | 0.999 | 1.000 | 1.000 | 2198 | 1026 |
| HG003 | 4.4.6 | 0.999 | 0.999 | 0.999 | 3511 | 3005 |
| HG003 | 4.5.4 | 0.999 | 0.999 | 0.999 | 2936 | 2338 |
| HG004 | 4.4.6 | 0.999 | 0.999 | 0.999 | 3748 | 2584 |
| HG004 | 4.5.4 | 0.999 | 1.000 | 0.999 | 2963 | 1803 |
| HG005 | 4.4.6 | 0.999 | 0.999 | 0.999 | 3023 | 2047 |
| HG005 | 4.5.4 | 0.999 | 1.000 | 0.999 | 2413 | 1369 |
| HG006 | 4.4.6 | 0.999 | 0.999 | 0.999 | 3103 | 2408 |
| HG006 | 4.5.4 | 0.999 | 1.000 | 0.999 | 2484 | 1699 |
| HG007 | 4.4.6 | 0.999 | 0.999 | 0.999 | 3467 | 2327 |
| HG007 | 4.5.4 | 0.999 | 1.000 | 0.999 | 2955 | 1602 |
Indels table (click to expand)
| Sample | Version | Recall | Precision | F1-score | FN | FP |
| ------ | ------- | ------ | --------- | -------- | ---- | ---- |
| HG001 | 4.4.6 | 0.996 | 0.997 | 0.997 | 1867 | 1437 |
| HG001 | 4.5.4 | 0.996 | 0.997 | 0.997 | 1849 | 1231 |
| HG002 | 4.4.6 | 0.996 | 0.997 | 0.997 | 2101 | 1421 |
| HG002 | 4.5.4 | 0.996 | 0.998 | 0.997 | 1998 | 1229 |
| HG003 | 4.4.6 | 0.996 | 0.997 | 0.997 | 1852 | 1420 |
| HG003 | 4.5.4 | 0.997 | 0.998 | 0.997 | 1789 | 1164 |
| HG004 | 4.4.6 | 0.996 | 0.997 | 0.997 | 1898 | 1384 |
| HG004 | 4.5.4 | 0.996 | 0.998 | 0.997 | 1877 | 1226 |
| HG005 | 4.4.6 | 0.998 | 0.998 | 0.998 | 897 | 670 |
| HG005 | 4.5.4 | 0.998 | 0.999 | 0.998 | 810 | 554 |
| HG006 | 4.4.6 | 0.997 | 0.998 | 0.998 | 1147 | 838 |
| HG006 | 4.5.4 | 0.997 | 0.998 | 0.998 | 1116 | 741 |
| HG007 | 4.4.6 | 0.997 | 0.998 | 0.998 | 1246 | 868 |
| HG007 | 4.5.4 | 0.997 | 0.998 | 0.998 | 1161 | 762 |
**HG002 T2TQ100 performance**
**DRAGEN**: 4.4.6 vs 4.5.4 | **Truthset**: T2TQ100-v1.1-v0.019 | **Reference**: GRCh38
HG002 T2TQ100-v1.1-v0.019 small variants comparison (click to expand)
| Version | SNPs FN | SNPs FP | SNPs FP+FN | Indels FN | Indels FP | Indels FP+FN |
| ------- | ------- | ------- | ---------- | --------- | --------- | ------------ |
| 4.4.6 | 21571 | 8752 | 30323 | 40208 | 23681 | 63889 |
| 4.5.4 | 16490 | 5764 | 22254 | 36945 | 19661 | 56606 |
**A legacy of continuous innovation and improving accuracy in each version.**
Historical HG002 benchmarked releases using the HG002 small variants NIST v4.2.1 truthset show FP+FN dropping from 41,244 in DRAGEN 3.4.5 to 4,364 in DRAGEN 4.5.4.
Historical version trend table (click to expand)
| Version | FP+FN |
| ------- | ------ |
| 3.4.5 | 41,244 |
| 3.5.7 | 40,056 |
| 3.6.3 | 39,046 |
| 3.7.5 | 21,479 |
| 3.8.4 | 20,402 |
| 3.9.3 | 19,052 |
| 3.10.4 | 12,851 |
| 4.0.3 | 12,815 |
| 4.2.4 | 11,163 |
| 4.3.3 | 6,615 |
| 4.4.6 | 5,955 |
| 4.5.4 | 4,364 |
**Mosaic detection**
Non-cancer post-zygotic mosaic variants have typical allele fraction (AFs) lower than 50% and therefore more challenging to find with the default small variant caller that has been optimized to detect germline variants with typical AFs of 0%, 50% or 100%. The Mosaic variant caller has been designed to address this gap by training a dedicated machine learning model trained on lowAF variants. For more information, refer to the [DRAGEN user guide](/dragen/dragen-v4.5/product-guides/dragen-v4.5/dragen-dna-pipeline/small-variant-calling/mosaic-detection.md).
**DRAGEN**: DRAGEN 4.5.4 vs 4.4.6 | **Truthset**: HG002 NIST Mosaic v1.0 | **Reference**: GRCh38 Results reported for HG002 sample [fastqs](https://ftp-trace.ncbi.nlm.nih.gov/ReferenceSamples/giab/data/AshkenazimTrio/HG002_NA24385_son/NIST_HiSeq_HG002_Homogeneity-10953946/HG002_HiSeq300x_fastq/) sequenced with HiSeq2500 at 300x available from NIST.
HG002 mosaic small variants comparison (click to expand)
| Version | SNPs FN | SNPs FP | SNPs TP | SNPs FP+FN | Indels FN | Indels FP | Indels TP | Indels FP+FN |
| ------- | ------- | ------- | ------- | ---------- | --------- | --------- | --------- | ------------ |
| 4.4.6 | 0 | 318 | 85 | 318 | 0 | 196 | 0 | 196 |
| 4.5.4 | 0 | 311 | 85 | 311 | 0 | 185 | 0 | 185 |
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