Is SCN1B p.Phe86= (c.258C>T) pathogenic?

SCN1B p.Phe86= (c.258C>T) is classified Likely benign in SCN1B (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-24). Ultra-rare (popmax 0.0165%, mid); Associated with Brugada syndrome 5.

What condition is associated with SCN1B p.Phe86= (c.258C>T)?

SCN1B p.Phe86= (c.258C>T) is associated with Brugada syndrome 5 (ClinVar).

How common is SCN1B p.Phe86= (c.258C>T) in the general population?

SCN1B p.Phe86= (c.258C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

How is Brugada syndrome inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

SCN1B p.Phe86=

c.258C>T · rs751009774 · VCV389010

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

Brugada syndrome 5

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 -7.9	GERP -3.4
Overall
CADD	0.873	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,060 alleles

Filtering AF 0.00164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.00217% 35/1,613,970 alleles · ultra-rare exomes 29/1,461,814 · genomes 6/152,156 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
South Asian	0.00439%	22,769
African / African-American	0.00267%	37,484
European (non-Finnish)	0.00237%	42,141

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: SCN1B
Protein: p.Phe86=
Coding: c.258C>T
MANE Select: NM_001037
dbSNP: rs751009774
Type: single nucleotide variant
Location: chr19:35033549 (GRCh38)
Gene constraint: LOEUF 0.71 · pLI 0.20 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 87.90 · 39 PDB
Residue 86: an α-helix; the ig-like c2-type domain

Full SCN1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Brugada syndrome 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Brugada syndrome (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

SCN1B p.Phe86Leu Uncertain significance ★★ ⚠ same residue
SCN1B c.449-2A>G Pathogenic ★★★ same condition
SCN1B c.449-1G>T Likely pathogenic ★★ same condition
SCN1B p.Arg85Cys Pathogenic/Likely pathogenic ★★ same condition
SCN1B p.Arg85His Pathogenic/Likely pathogenic ★★ ⚠ same condition
SCN1B p.Val158Met Pathogenic/Likely pathogenic ★★ ⚠ same condition
SCN1B c.448+100G>T Uncertain significance ★★ same condition
SCN1B c.448+103C>T 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/scn1b-p-phe86 (accessed [today's date]).

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