Is SCN2A p.Phe1755fs (c.5265_5268del) pathogenic?

SCN2A p.Phe1755fs (c.52655268del) is classified Likely pathogenic in SCN2A (ClinVar, Single submitter, 1 submitter; last evaluated 2018-11-28). No gnomAD frequency available for this variant; Associated with Inborn genetic diseases.

What condition is associated with SCN2A p.Phe1755fs (c.5265_5268del)?

SCN2A p.Phe1755fs (c.5265_5268del) is associated with Inborn genetic diseases (ClinVar).

How common is SCN2A p.Phe1755fs (c.5265_5268del) in the general population?

SCN2A p.Phe1755fs (c.5265_5268del) is no gnomAD frequency available for this variant (gnomAD).

SCN2A p.Phe1755fs

c.5265_5268del · rs1466129143 · VCV985489

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	escapes	premature termination codon in the last exon (27 of 27) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.2	GERP 1.1, 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: SCN2A
Protein: p.Phe1755fs
Coding: c.5265_5268del
MANE Select: NM_001040142
dbSNP: rs1466129143
Type: Deletion
Location: chr2:165389069 (GRCh38)
Gene constraint: LOEUF 0.161 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 69.28 · 5 PDB
Residue 1755: a UniProt-annotated variant site (found in a patient with intractable epilepsy and severe mental decline; likely pathogenic; non-conducting; loss of voltage-gated sodium channel activity; dominant-negative); a UniProt-annotated variant site (found in a patient with schizofrenia; uncertain significance); a UniProt-annotated variant site (found in a patient with autism spectrum disorder; likely pathogenic); a UniProt-annotated variant site (found in a patient with autism spectrum disorder; likely pathogenic; loss of voltage-gated sodium channel activity; non-conducting); a UniProt-annotated variant site (in dee11); an α-helix

Full SCN2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SCN2A p.Phe1661fs Pathogenic/Likely pathogenic ★★ same condition
SCN2A p.Ala30fs Pathogenic ★ same condition
SCN2A p.Ala631fs Pathogenic ★ same condition
SCN2A p.Cys1366fs Pathogenic ★ same condition
SCN2A p.Glu1023fs Pathogenic ★ same condition
SCN2A p.Ile1469fs Pathogenic ★ same condition
SCN2A p.Leu1585fs Pathogenic ★ same condition
SCN2A p.Phe1463fs Pathogenic ★ 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/scn2a-p-phe1755fs (accessed [today's date]).

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