Is SCN8A p.Ter1981= (c.5943GAG[1]) pathogenic?

SCN8A p.Ter1981= (c.5943GAG[1]) is classified Benign/Likely benign in SCN8A (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-03). Rare (popmax 0.693%, afr); Associated with early-infantile DEE.

What condition is associated with SCN8A p.Ter1981= (c.5943GAG[1])?

SCN8A p.Ter1981= (c.5943GAG[1]) is associated with early-infantile DEE (ClinVar).

How common is SCN8A p.Ter1981= (c.5943GAG[1]) in the general population?

SCN8A p.Ter1981= (c.5943GAG[1]) is rare (popmax 0.693%, afr) (gnomAD).

SCN8A p.Ter1981=

c.5943GAG[1] · rs555793953 · VCV196030

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.693%, afr)

Conditions

early-infantile DEE

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function in a LoF-intolerant gene
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.4	GERP 2.8, phastCons 1
Overall
CADD	7.039	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.693% African / African-American · 518/74,792 alleles

Filtering AF 0.643% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.624%

Overall 0.0371% 595/1,604,900 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.693%	144
Middle Eastern	0.0826%	1,210
Admixed American	0.0564%	1,773
Remaining individualsnot grpmax-eligible	0.045%	2,222
South Asian	0.00334%	29,950
European (non-Finnish)	0.000681%	146,897

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: SCN8A
Protein: p.Ter1981=
Coding: c.5943GAG[1]
MANE Select: NM_001330260
dbSNP: rs555793953
Type: Microsatellite
Location: chr12:51807429 (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

Disease context

early-infantile DEE — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SCN8A p.Ter1981LeuextTer? Uncertain significance ★ same residue
SCN8A p.Leu503_Ser504insTer Pathogenic ★★ same condition
SCN8A p.Arg1968fs Uncertain significance ★★ same condition
SCN8A p.Tyr1580del Uncertain significance ★★ same condition
SCN8A c.2132-8_2132-5del Likely benign ★★ same condition
SCN8A c.277-23TC[2] Likely benign ★★ same condition
SCN8A c.277-10_277-7del Conflicting classifications of pathogenicity ★ same condition
SCN8A c.706+5_706+6del Uncertain significance ★ same condition

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-ter1981 (accessed [today's date]).

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