Is SCN9A p.His1069= (c.3207C>T) pathogenic?

SCN9A p.His1069= (c.3207C>T) is classified Likely benign in SCN9A (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-05). Ultra-rare (popmax 0.0342%, nfe); Associated with generalized epilepsy with febrile seizures plus, type 7.

What condition is associated with SCN9A p.His1069= (c.3207C>T)?

SCN9A p.His1069= (c.3207C>T) is associated with generalized epilepsy with febrile seizures plus, type 7, neuropathy, hereditary sensory and autonomic, type 2A (ClinVar).

How common is SCN9A p.His1069= (c.3207C>T) in the general population?

SCN9A p.His1069= (c.3207C>T) is ultra-rare (popmax 0.0342%, nfe) (gnomAD).

How is Genetic epilepsy with febrile seizure plus inherited?

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

SCN9A p.His1069=

c.3207C>T · rs200689065 · VCV387818

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0342%, nfe)

Conditions

generalized epilepsy with febrile seizures plus, type 7

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.057	GERP -4.2
Overall
CADD	1.309	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0342% European (non-Finnish) · 404/1,179,718 alleles

Filtering AF 0.0315% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0304%

Overall 0.0266% 429/1,613,348 alleles · ultra-rare exomes 414/1,461,314 · genomes 15/152,034 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0342%	2,920
Remaining individualsnot grpmax-eligible	0.0192%	5,203
Finnishnot grpmax-eligible	0.0141%	7,106
African / African-American	0.00401%	24,960
South Asian	0.0011%	91,068

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: SCN9A
Protein: p.His1069=
Coding: c.3207C>T
MANE Select: NM_001365536
dbSNP: rs200689065
Type: single nucleotide variant
Location: chr2:166272543 (GRCh38)

Full SCN9A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

generalized epilepsy with febrile seizures plus, type 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: neuropathy, hereditary sensory and autonomic, type 2A

For Genetic epilepsy with febrile seizure plus (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood

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/scn9a-p-his1069 (accessed [today's date]).

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