Is SCN1B p.Phe67= (c.201T>C) pathogenic?

SCN1B p.Phe67= (c.201T>C) is classified Likely benign in SCN1B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-09). Absent from gnomAD v4.1; Associated with Brugada syndrome 5.

What condition is associated with SCN1B p.Phe67= (c.201T>C)?

SCN1B p.Phe67= (c.201T>C) is associated with Brugada syndrome 5 (ClinVar).

How common is SCN1B p.Phe67= (c.201T>C) in the general population?

SCN1B p.Phe67= (c.201T>C) is absent from gnomAD v4.1 (gnomAD).

How is Brugada syndrome inherited?

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

SCN1B p.Phe67=

c.201T>C · rs2514233178 · VCV2015396

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Brugada syndrome 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.018	GERP -2, phastCons 0.94
Overall
CADD	11.04	PHRED · no single calibrated threshold — expert panels disagree

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: SCN1B
Protein: p.Phe67=
Coding: c.201T>C
MANE Select: NM_001037
dbSNP: rs2514233178
Type: single nucleotide variant
Location: chr19:35032688 (GRCh38)
Gene constraint: LOEUF 0.71 · pLI 0.20 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 87.90 · 39 PDB
Residue 67: 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 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
SCN1B c.448+10G>C 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-phe67 (accessed [today's date]).

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