Is SCN2B p.Arg28= (c.82C>A) pathogenic?

SCN2B p.Arg28= (c.82C>A) is classified Likely benign in SCN2B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-26). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with SCN2B p.Arg28= (c.82C>A)?

SCN2B p.Arg28= (c.82C>A) is associated with Cardiovascular phenotype (ClinVar).

How common is SCN2B p.Arg28= (c.82C>A) in the general population?

SCN2B p.Arg28= (c.82C>A) is absent from gnomAD v4.1 (gnomAD).

SCN2B p.Arg28=

c.82C>A · rs17121819 · VCV2562615

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Cardiovascular phenotype

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 0.007	GERP -0.12
Overall
CADD	3.525	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: SCN2B
Protein: p.Arg28=
Coding: c.82C>A
MANE Select: NM_004588
dbSNP: rs17121819
Type: single nucleotide variant
Location: chr11:118168740 (GRCh38)
Gene constraint: LOEUF 1.15 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.03 · 35 PDB
Residue 28: a UniProt-annotated variant site (in atfb14; the mutant results in reduced sodium currents and altered channel gating when coexpressed with scn5a in a heterologous expression system)

Full SCN2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SCN2B p.Arg28Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
SCN2B p.Arg28Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
SCN2B p.Ala171Pro Uncertain significance ★★ ⚠ same condition
SCN2B p.Arg137His Uncertain significance ★★ ⚠ same condition
SCN2B p.Arg185Thr Uncertain significance ★★ ⚠ same condition
SCN2B p.Arg84Cys Uncertain significance ★★ ⚠ same condition
SCN2B p.Arg98Gly Uncertain significance ★★ ⚠ same condition
SCN2B p.Asp109Asn 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/scn2b-p-arg28 (accessed [today's date]).

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