Is CELF2 p.Pro520Ser (c.1558C>T) pathogenic?

CELF2 p.Pro520Ser (c.1558C>T) is classified Pathogenic in CELF2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-10-06). AlphaMissense: likely pathogenic (0.9905); Absent from gnomAD v4.1; Associated with developmental and epileptic encephalopathy 97.

What condition is associated with CELF2 p.Pro520Ser (c.1558C>T)?

CELF2 p.Pro520Ser (c.1558C>T) is associated with developmental and epileptic encephalopathy 97 (ClinVar).

How common is CELF2 p.Pro520Ser (c.1558C>T) in the general population?

CELF2 p.Pro520Ser (c.1558C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CELF2 p.Pro520Ser (c.1558C>T)?

AlphaMissense predicts likely pathogenic (score 0.9905) — an in-silico prediction, not a clinical call.

CELF2 p.Pro520Ser

c.1558C>T · rs2132786780 · VCV1299463

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9905 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy 97

Computational evidence

Protein change
AlphaMissense	0.9905	likely pathogenic ✓ concordant with ClinVar
REVEL	0.711	pathogenic-leaning
SaProt	LLR -12.96	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.7, phastCons 1
Regional constraint	o/e 0.27	constrained · MANE · 7,704 bp · p 1.9e-16 · regional, not allelic
Overall
CADD	26.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P507S vs ClinVar P520S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CELF2
Protein: p.Pro520Ser
Coding: c.1558C>T
MANE Select: NM_001326342
dbSNP: rs2132786780
Type: single nucleotide variant
Location: chr10:11329045 (GRCh38)
Gene constraint: LOEUF 0.294 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.26 · 7 PDB

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 p.Pro520Leu Uncertain significance ⚠ same residue
CELF2 p.Arg513His Likely pathogenic ★★ same condition
CELF2 p.Gln237Ter Pathogenic/Likely pathogenic ★★ same condition
CELF2 p.Arg506His Pathogenic ★ same condition
CELF2 p.Arg513Cys Likely pathogenic ★ same condition
CELF2 c.74+5189A>C Uncertain significance ★ same condition
CELF2 p.Cys15Ter Uncertain significance ★ same condition
CELF2 p.Gly249Val 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/celf2-p-pro520ser (accessed [today's date]).

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