Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_001330260.2(SCN8A):c.5795G>C (p.Arg1932Pro)

CA318305

207134 (ClinVar)

Gene: SCN8A (HGNC:6334)

Condition: complex neurodevelopmental disorder (MONDO:0100038)

Inheritance Mode: Autosomal dominant inheritance

UUID: 2a80ec23-1208-46a6-9e9c-740e0bd96689

Approved on: 2026-06-23

Published on: 2026-07-28

HGVS expressions

NM_001330260.2:c.5795G>C

NM_001330260.2(SCN8A):c.5795G>C (p.Arg1932Pro)

NC_000012.12:g.51807281G>C

CM000674.2:g.51807281G>C

NC_000012.11:g.52201065G>C

CM000674.1:g.52201065G>C

NC_000012.10:g.50487332G>C

NG_021180.2:g.221046G>C

NG_021180.3:g.222324G>C

ENST00000354534.11:c.5795G>C

ENST00000627620.5:c.5795G>C

ENST00000662684.1:c.5795G>C

ENST00000668547.1:c.5672G>C

ENST00000354534.10:c.5795G>C

ENST00000355133.7:c.5672G>C

ENST00000545061.5:c.5672G>C

ENST00000599343.5:c.5828G>C

ENST00000627620.2:c.5795G>C

NM_001177984.2:c.5672G>C

NM_014191.3:c.5795G>C

NM_001330260.1:c.5795G>C

NM_001369788.1:c.5672G>C

NM_014191.4:c.5795G>C

NM_001177984.3:c.5672G>C

Likely Benign

BP4 BS1

PP3 PM5 PM1 PS4

Evidence Links 0

Expert Panel

Epilepsy Sodium Channel VCEP

Criteria Specification Information

Criteria Specification: ClinGen Epilepsy Sodium Channel Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for SCN8A Version 2.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Epilepsy Sodium Channel VCEP

The c.5795G>C variant in SCN8A is a missense variant predicted to cause substitution of Arginine by Proline at amino acid 1932 (p.Arg1932Pro). The total allele frequency in GnomAD 4.1.1 is 0.006754% (109/1613768 alleles), which is higher than the ClinGen Sodium Channel VCEP threshold (0.0002%) for BS1, and therefore meets this criterion (BS1). The computational predictor REVEL gives a score of 0.248, which suggests that the variant does not impact SCN8A function (BP4). In summary, this variant meets the criteria to be classified as likely benign for autosomal dominant complex neurodevelopmental disorder based on the ACMG/AMP criteria applied, as specified by the ClinGen Epilepsy Sodium Channel VCEP: BS1, BP4 (VCEP SCN8A specifications v2.0.0; June 23, 2026).

BP4

Revel= 0.248

BS1

Total allele frequency in GnomAD 4.1.1 is 0.006754%, which is higher than the ClinGen Epilepsy Sodium Channel VCEP threshold (>0.0002%) for BS1, and therefore meets this criterion (BS1).

PP3

Revel= 0.248

PM5

Different missense variants at this codon in SCN8A or paralogous genes have been identified but do not meet the classification of pathogenic or likely pathogenic by the ClinGen Epilepsy Sodium Channel VCEP. SCN8A c.5795G>A (p.Arg1932Gln)= Likely benign (BS1+BP4) SCN2A c.5878C>T (p.Pro1960Ser)= VUS (PM2_sup) SCN3A c.5863C>T (p.Pro1955Ser)= VUS (PM2_sup)

PM1

Not in Pathogenic Enriched Region

PS4

SCV002647299.2= Ambry- Likely Benign SCV006072489.1/SCV000633977.10= Labcorp- VUS SCV001247161.37= Tuebingen- VUS SCV000242925.11= GeneDX- Likely Benign

Curation History

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