Is CELF2 p.Lys466fs (c.1395_1396del) pathogenic?

CELF2 p.Lys466fs (c.13951396del) is classified Likely pathogenic in CELF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-28). Associated with developmental and epileptic encephalopathy 97.

What condition is associated with CELF2 p.Lys466fs (c.1395_1396del)?

CELF2 p.Lys466fs (c.1395_1396del) is associated with developmental and epileptic encephalopathy 97 (ClinVar).

CELF2 p.Lys466fs

c.1395_1396del · VCV4854577

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

developmental and epileptic encephalopathy 97

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 LoF-intolerant gene
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (12 of 13, 43 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.7, phastCons 1

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

Variant & gene context

Gene: CELF2
Protein: p.Lys466fs
Coding: c.1395_1396del
MANE Select: NM_001326342
Type: Deletion
Location: chr10:11325936 (GRCh38)
Gene constraint: LOEUF 0.294 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.26 · 7 PDB
Residue 466: the rrm 3 domain; a β-strand; the 'necessary for rna-binding, tnnt2 exon 5 and nmda r1 exon 21 inclusion' region

Full CELF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

developmental and epileptic encephalopathy 97 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CELF2 c.355-6858_403+3281del Pathogenic ★ same condition
CELF2 p.Ala295fs Pathogenic ★ same condition
CELF2 p.Asp451fs Pathogenic ★ same condition
CELF2 p.Lys471fs Likely pathogenic ★ same condition
CELF2 p.Met13fs Likely pathogenic ★ same condition
CELF2 c.355-48_403+52del Uncertain significance ★ same condition
CELF2 p.Ala363_Leu364insTer Uncertain significance ★ same condition
CELF2 p.Arg513His Likely 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/celf2-p-lys466fs (accessed [today's date]).

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