Is SCN2B p.Pro119= (c.357G>A) pathogenic?

SCN2B p.Pro119= (c.357G>A) is classified Likely benign in SCN2B (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-04-19). Ultra-rare (popmax 0.0134%, eas); Associated with Cardiovascular phenotype.

What condition is associated with SCN2B p.Pro119= (c.357G>A)?

SCN2B p.Pro119= (c.357G>A) is associated with Cardiovascular phenotype, atrial fibrillation, familial, 14 (ClinVar).

How common is SCN2B p.Pro119= (c.357G>A) in the general population?

SCN2B p.Pro119= (c.357G>A) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

SCN2B p.Pro119=

c.357G>A · rs149169244 · VCV512603

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2.8	GERP -4.3
Overall
CADD	6.209	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% East Asian · 6/44,884 alleles

Filtering AF 0.00842% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00787%

Overall 0.01% 162/1,614,222 alleles · ultra-rare exomes 150/1,461,890 · genomes 12/152,332 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0328%	3,050
Remaining individualsnot grpmax-eligible	0.0176%	5,683
East Asiangrpmax	0.0134%	7,481
European (non-Finnish)	0.00991%	10,086
Admixed American	0.005%	20,010
African / African-American	0.00266%	37,525
South Asian	0.0022%	45,541

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro119=
Coding: c.357G>A
MANE Select: NM_004588
dbSNP: rs149169244
Type: single nucleotide variant
Location: chr11:118168176 (GRCh38)
Gene constraint: LOEUF 1.15 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.03 · 35 PDB
Residue 119: an α-helix; 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.Pro119Leu Likely benign ★★ same residue
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

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-pro119 (accessed [today's date]).

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