Is CELF2 p.Gly249Val (c.746G>T) pathogenic?

CELF2 p.Gly249Val (c.746G>T) is classified Uncertain significance in CELF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-05). AlphaMissense: ambiguous (0.5192); Absent from gnomAD v4.1; Associated with developmental and epileptic encephalopathy 97.

What condition is associated with CELF2 p.Gly249Val (c.746G>T)?

CELF2 p.Gly249Val (c.746G>T) is associated with developmental and epileptic encephalopathy 97 (ClinVar).

How common is CELF2 p.Gly249Val (c.746G>T) in the general population?

CELF2 p.Gly249Val (c.746G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CELF2 p.Gly249Val (c.746G>T)?

AlphaMissense predicts ambiguous (score 0.5192) — an in-silico prediction, not a clinical call.

CELF2 p.Gly249Val

c.746G>T · rs2548891766 · VCV2505351

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5192 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,511,754)

Conditions

developmental and epileptic encephalopathy 97

Computational evidence

Protein change
AlphaMissense	0.5192	ambiguous
REVEL	0.45	indeterminate
SaProt	LLR -12.67	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.50	unconstrained · MANE · 156 kb · p 7.3e-29 · regional, not allelic
Overall
CADD	32.0	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 G242V vs ClinVar G249V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,511,754). 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: CELF2
Protein: p.Gly249Val
Coding: c.746G>T
MANE Select: NM_001326342
dbSNP: rs2548891766
Type: single nucleotide variant
Location: chr10:11270793 (GRCh38)
Gene constraint: LOEUF 0.294 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.26 · 7 PDB
Residue 249: 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 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.Gly503Ser Uncertain significance ★ ⚠ same condition
CELF2 p.Phe97Val 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-gly249val (accessed [today's date]).

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