Is SCN2B p.Asp45= (c.135C>T) pathogenic?

SCN2B p.Asp45= (c.135C>T) is classified Likely benign in SCN2B (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-18). Ultra-rare (popmax 0.0165%, mid); Associated with Cardiovascular phenotype.

What condition is associated with SCN2B p.Asp45= (c.135C>T)?

SCN2B p.Asp45= (c.135C>T) is associated with Cardiovascular phenotype, atrial fibrillation, familial, 14 (ClinVar).

How common is SCN2B p.Asp45= (c.135C>T) in the general population?

SCN2B p.Asp45= (c.135C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

SCN2B p.Asp45=

c.135C>T · rs533110688 · VCV510784

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

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 -2.5	GERP -3.9
Overall
CADD	6.166	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.00722% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00549%

Overall 0.00285% 46/1,614,208 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
African / African-American	0.0133%	7,505
East Asian	0.0111%	8,977
South Asian	0.00659%	15,180
Remaining individualsnot grpmax-eligible	0.0064%	15,627
Admixed American	0.00333%	30,018
European (non-Finnish)	0.00153%	65,557

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: SCN2B
Protein: p.Asp45=
Coding: c.135C>T
MANE Select: NM_004588
dbSNP: rs533110688
Type: single nucleotide variant
Location: chr11:118168687 (GRCh38)
Gene constraint: LOEUF 1.15 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.03 · 35 PDB
Residue 45: the ig-like c2-type domain

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

Also linked: atrial fibrillation, familial, 14

Similar variants

SCN2B p.Ala171Pro Uncertain significance ★★ ⚠ same condition
SCN2B p.Arg135Cys Uncertain significance ★★ ⚠ same condition
SCN2B p.Arg137His Uncertain significance ★★ ⚠ same condition
SCN2B p.Arg154Gln Uncertain significance ★★ ⚠ same condition
SCN2B p.Arg185Thr Uncertain significance ★★ ⚠ same condition
SCN2B p.Arg84Cys Uncertain significance ★★ ⚠ same condition
SCN2B p.Arg98Cys Uncertain significance ★★ ⚠ same condition
SCN2B p.Arg98Gly 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-asp45 (accessed [today's date]).

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