Is SCN2B p.Pro25fs (c.73_74delinsG) pathogenic?

SCN2B p.Pro25fs (c.7374delinsG) is classified Uncertain significance in SCN2B (ClinVar, Single submitter, 1 submitter; last evaluated 2020-08-03). No gnomAD frequency available for this variant; Associated with Cardiovascular phenotype.

What condition is associated with SCN2B p.Pro25fs (c.73_74delinsG)?

SCN2B p.Pro25fs (c.73_74delinsG) is associated with Cardiovascular phenotype (ClinVar).

How common is SCN2B p.Pro25fs (c.73_74delinsG) in the general population?

SCN2B p.Pro25fs (c.73_74delinsG) is no gnomAD frequency available for this variant (gnomAD).

SCN2B p.Pro25fs

c.73_74delinsG · rs1043620518 · VCV1758214

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 4
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.7	GERP 1.9, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SCN2B
Protein: p.Pro25fs
Coding: c.73_74delinsG
MANE Select: NM_004588
dbSNP: rs1043620518
Type: Indel
Location: chr11:118168748 (GRCh38)
Gene constraint: LOEUF 1.15 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.03 · 35 PDB

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.Pro25Ala Uncertain significance ★ ⚠ same residue
SCN2B p.Asn209Pro Conflicting classifications of pathogenicity ★ same condition
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-pro25fs (accessed [today's date]).

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