Is SCN8A p.Arg628= (c.1884C>T) pathogenic?

SCN8A p.Arg628= (c.1884C>T) is classified Likely benign in SCN8A (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-01). Absent from gnomAD v4.1.

How common is SCN8A p.Arg628= (c.1884C>T) in the general population?

SCN8A p.Arg628= (c.1884C>T) is absent from gnomAD v4.1 (gnomAD).

SCN8A p.Arg628=

c.1884C>T · rs1387548452 · VCV1335106

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.1	GERP -0.17, phastCons 1
Overall
CADD	13.52	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SCN8A
Protein: p.Arg628=
Coding: c.1884C>T
MANE Select: NM_001330260
dbSNP: rs1387548452
Type: single nucleotide variant
Location: chr12:51721794 (GRCh38)
Gene constraint: LOEUF 0.189 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.90 · 7 PDB

Full SCN8A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SCN8A p.Arg628Leu Uncertain significance ★★ ⚠ same residue
SCN8A p.Arg628His Uncertain significance ★ ⚠ same residue
SCN8A p.Arg628Pro Uncertain significance ★ same residue
SCN8A c.615-1G>A Pathogenic ★★★ same type
SCN8A p.Arg1872Gln Pathogenic ★★★ ⚠ same type
SCN8A p.Asn1318Ser Likely pathogenic ★★★ same type
SCN8A p.Asn418Asp Likely pathogenic ★★★ same type
SCN8A p.Glu1218Lys Pathogenic ★★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/scn8a-p-arg628 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown