Is CELF2 p.Val95Leu (c.283G>T) pathogenic?

CELF2 p.Val95Leu (c.283G>T) is classified Uncertain significance in CELF2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-29). AlphaMissense: likely pathogenic (0.8546); Absent from gnomAD v4.1.

How common is CELF2 p.Val95Leu (c.283G>T) in the general population?

CELF2 p.Val95Leu (c.283G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CELF2 p.Val95Leu (c.283G>T)?

AlphaMissense predicts likely pathogenic (score 0.8546) — an in-silico prediction, not a clinical call.

CELF2 p.Val95Leu

c.283G>T · rs577233700 · VCV3233915

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8546 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8546	likely pathogenic
REVEL	0.296	indeterminate
SaProt	LLR -7.19	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
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	27.3	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 V88L vs ClinVar V95L) — 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.Val95Leu
Coding: c.283G>T
MANE Select: NM_001326342
dbSNP: rs577233700
Type: single nucleotide variant
Location: chr10:11217436 (GRCh38)
Gene constraint: LOEUF 0.294 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.26 · 7 PDB
Residue 95: the rrm 1 domain; an α-helix; 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

Similar variants

CELF2 p.Arg506Cys Pathogenic/Likely pathogenic ★★ same type
CELF2 p.Arg513His Likely pathogenic ★★ same type
CELF2 p.Gln237Ter Pathogenic/Likely pathogenic ★★ same type
CELF2 p.Ala135Thr Uncertain significance ★★ ⚠ same type
CELF2 p.Arg506His Pathogenic ★ same type
CELF2 p.Arg506Leu Pathogenic ★ same type
CELF2 p.Arg513Cys Likely pathogenic ★ same type
CELF2 c.53+1G>A Uncertain significance ★ same type

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-val95leu (accessed [today's date]).

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