Is SCN4A p.Leu796Val (c.2386C>G) pathogenic?

SCN4A p.Leu796Val (c.2386C>G) is classified Pathogenic/Likely pathogenic in SCN4A (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-21). AlphaMissense: likely pathogenic (0.9789); Absent from gnomAD v4.1; Associated with hyperkalemic periodic paralysis.

What condition is associated with SCN4A p.Leu796Val (c.2386C>G)?

SCN4A p.Leu796Val (c.2386C>G) is associated with hyperkalemic periodic paralysis (ClinVar).

How common is SCN4A p.Leu796Val (c.2386C>G) in the general population?

SCN4A p.Leu796Val (c.2386C>G) is absent from gnomAD v4.1 (gnomAD).

How is Hyperkalemic periodic paralysis inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about SCN4A p.Leu796Val (c.2386C>G)?

AlphaMissense predicts likely pathogenic (score 0.9789) — an in-silico prediction, not a clinical call.

SCN4A p.Leu796Val

c.2386C>G · rs750053946 · VCV383923

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.9789 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hyperkalemic periodic paralysis

Computational evidence

Protein change
AlphaMissense	0.9789	likely pathogenic ✓ concordant with ClinVar
REVEL	0.854	moderately pathogenic-leaning
SaProt	LLR -12.75	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.7	GERP 1.3, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 32 kb · p 7.8e-08 · regional, not allelic
Overall
CADD	22.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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: SCN4A
Protein: p.Leu796Val
Coding: c.2386C>G
dbSNP: rs750053946
Type: single nucleotide variant
Location: chr17:63951891 (GRCh38)

Full SCN4A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hyperkalemic periodic paralysis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hyperkalemic periodic paralysis (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Europe)

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/scn4a-p-leu796val (accessed [today's date]).

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