Is SCN8A p.Asp192= (c.576C>T) pathogenic?

SCN8A p.Asp192= (c.576C>T) is classified Benign in SCN8A (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-02-04). Common (popmax 99.5%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Inborn genetic diseases.

SCN8A p.Asp192=

Q: What condition is associated with SCN8A p.Asp192= (c.576C>T)?

SCN8A p.Asp192= (c.576C>T) is associated with Inborn genetic diseases, cognitive impairment with or without cerebellar ataxia, developmental and epileptic encephalopathy, 13 (ClinVar).

Q: How common is SCN8A p.Asp192= (c.576C>T) in the general population?

SCN8A p.Asp192= (c.576C>T) is common (popmax 99.5%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.576C>T · rs4761829 · VCV130253

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

gnomAD v4.1

Common

common (popmax 99.5%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.41	GERP -3.7, phastCons 0.16
Overall
CADD	6.889	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 99.5% East Asian · 44,641/44,876 alleles

Filtering AF 98.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 98.4%

Overall 85.3% 1,375,050/1,612,864 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	99.5%	1
Amishnot grpmax-eligible	92.2%	1
Finnishnot grpmax-eligible	91.4%	1
Admixed American	90.3%	1
European (non-Finnish)	86.9%	1
Remaining individualsnot grpmax-eligible	84.5%	1
Ashkenazi Jewishnot grpmax-eligible	80.7%	1
Middle Eastern	77.2%	1
South Asian	68%	1
African / African-American	65%	2

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.Asp192=
Coding: c.576C>T
MANE Select: NM_001330260
dbSNP: rs4761829
Type: single nucleotide variant
Location: chr12:51687181 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cognitive impairment with or without cerebellar ataxia developmental and epileptic encephalopathy, 13 seizures, benign familial infantile, 5 myoclonus, familial, 2 early-infantile DEE

Similar variants

SCN8A c.615-1G>A Pathogenic ★★★ same condition
SCN8A p.Arg1872Gln Pathogenic ★★★ ⚠ same condition
SCN8A p.Asn1318Ser Likely pathogenic ★★★ same condition
SCN8A p.Asn418Asp Likely pathogenic ★★★ same condition
SCN8A p.Glu1218Lys Pathogenic ★★★ same condition
SCN8A p.Ile1631Thr Likely pathogenic ★★★ same condition
SCN8A p.Ser845Cys Likely pathogenic ★★★ ⚠ same condition
SCN8A p.Ser845Phe Likely pathogenic ★★★ ⚠ 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-asp192 (accessed [today's date]).

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