PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome: genes and variants
Explore variant evidence for PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome across 1 analyzed protein (PURA). Linked ClinVar records include 27 pathogenic or likely pathogenic variants, 51 variants of uncertain significance and 14 with conflicting classifications.
Coverage includes proteins already analyzed in CATVariant, not every gene involved in this condition. Database links are associations, not an assessment of clinical gene–disease validity. Computable evidence prioritizes variants for expert review and does not reclassify them. Counts refer to the selected disease label.
Data updated 2026-10-15. Automated aggregation, not a clinical review date.
Download variant evidence (CSV)
Genes linked to PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome
PURA: Transcriptional activator protein Pur-alpha
27 ClinVar pathogenic / likely pathogenic and 65 uncertain variants in PURA have source records linked to PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome. Association strength is not clinical gene validity.
Where PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome variants cluster
- PURA PUR repeat II (positions 142–213): 13 of 27 ClinVar pathogenic / likely pathogenic variants, 2.1× more than its size predicts.
ClinVar pathogenic and likely pathogenic variants linked to PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| PURA G165S | 165 | PUR repeat II | Pathogenic / likely pathogenic (★★) |
| PURA R171G | 171 | PUR repeat II | Pathogenic / likely pathogenic (★★) |
| PURA M1V | 1 | Pathogenic / likely pathogenic (★★) | |
| PURA A89P | 89 | PUR repeat I | Pathogenic / likely pathogenic (★★) |
| PURA K144E | 144 | PUR repeat II | Pathogenic / likely pathogenic (★★) |
| PURA K160E | 160 | PUR repeat II | Pathogenic / likely pathogenic (★★) |
| PURA I188T | 188 | PUR repeat II | Pathogenic / likely pathogenic (★★) |
| PURA R199P | 199 | PUR repeat II | Pathogenic / likely pathogenic (★★) |
| PURA F231C | 231 | PUR repeat III | Pathogenic / likely pathogenic (★★) |
| PURA P260R | 260 | PUR repeat III | Pathogenic / likely pathogenic (★★) |
| PURA M1I | 1 | Pathogenic / likely pathogenic (★) | |
| PURA M1T | 1 | Pathogenic / likely pathogenic (★) | |
| PURA D76A | 76 | PUR repeat I | Pathogenic / likely pathogenic (★) |
| PURA D76V | 76 | PUR repeat I | Pathogenic / likely pathogenic (★) |
| PURA G165C | 165 | PUR repeat II | Pathogenic / likely pathogenic (★) |
| PURA R171P | 171 | PUR repeat II | Pathogenic / likely pathogenic (★) |
| PURA M1L | 1 | Pathogenic / likely pathogenic (★) | |
| PURA F73V | 73 | PUR repeat I | Pathogenic / likely pathogenic (★) |
| PURA L168P | 168 | PUR repeat II | Pathogenic / likely pathogenic (★) |
| PURA R72P | 72 | PUR repeat I | Pathogenic / likely pathogenic (★) |
| PURA K87E | 87 | PUR repeat I | Pathogenic / likely pathogenic (★) |
| PURA L100P | 100 | PUR repeat I | Pathogenic / likely pathogenic (★) |
| PURA A189P | 189 | PUR repeat II | Pathogenic / likely pathogenic (★) |
| PURA L202P | 202 | PUR repeat II | Pathogenic / likely pathogenic (★) |
| PURA S237F | 237 | PUR repeat III | Pathogenic / likely pathogenic (★) |
| PURA R166C | 166 | PUR repeat II | Pathogenic / likely pathogenic |
| PURA I206F | 206 | PUR repeat II | Pathogenic / likely pathogenic |
Uncertain variants prioritized for review in PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| PURA G165R | 165 | PUR repeat II | Conflicting reports (★) | +6: 4 other pathogenic changes within 3 positions; G165C at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 1.00 |
| PURA R199C | 199 | PUR repeat II | Conflicting reports (★) | +6: 2 other pathogenic changes within 3 positions; R199P at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 1.00 |
| PURA R72H | 72 | PUR repeat I | Uncertain (★) | +6: 2 other pathogenic changes within 3 positions; R72P at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 1.00 |
Which prediction tools work for PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome
Observed separation of ClinVar pathogenic / likely pathogenic from benign / likely benign variants (AUROC × 100). This benchmark is not a clinical recommendation.
- CATVariant: 97 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- ESM1b (LLR): 96 out of 100
- AlphaMissense: 95 out of 100
- PolyPhen-2: 94 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- MutPred2: 94 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 90 out of 100
- MetaSVM: 77 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- MetaLR: 67 out of 100 (learned from overlapping clinical labels, so this is optimistic)
Frequently asked questions
Which genes have records linked to PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome?
This view contains 1 analyzed proteins: PURA. Links come from clinical records and association databases. They do not imply that every listed gene is a validated cause, and missing genes may not yet be analyzed.
What do the clinical classifications mean?
Linked records include 27 pathogenic or likely pathogenic variants, 51 variants of uncertain significance and 14 with conflicting classifications. Labels summarize source records; multi-condition records may not make a separate assertion for this disease. Check the original record and review status.
Does the evidence score change a VUS classification?
No. 3 VUS or conflicting variants reach the likely-pathogenic points range on the computable criteria available here. This is a research prioritization signal, not a clinical classification. Patient, family and other required evidence may be missing.
Can I download the variant evidence?
Download the CSV for all 163 variants in the selected disease scope, including clinical labels, review status, evidence criteria, predictor scores, functional measurements and population frequency where available.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from eligible public CATVariant analyses of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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