Is CELF4 p.Arg138Ter (c.412C>T) pathogenic?

CELF4 p.Arg138Ter (c.412C>T) is classified Uncertain significance in CELF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-24). Absent from gnomAD v4.1; Associated with neurodevelopmental disorder.

What condition is associated with CELF4 p.Arg138Ter (c.412C>T)?

CELF4 p.Arg138Ter (c.412C>T) is associated with neurodevelopmental disorder (ClinVar).

How common is CELF4 p.Arg138Ter (c.412C>T) in the general population?

CELF4 p.Arg138Ter (c.412C>T) is absent from gnomAD v4.1 (gnomAD).

CELF4 p.Arg138Ter

c.412C>T · VCV3362798

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

neurodevelopmental disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 13
REVEL	0.096	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.4, phastCons 1
Overall
CADD	50.0	PHRED · no single calibrated threshold — expert panels disagree

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

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: CELF4
Protein: p.Arg138Ter
Coding: c.412C>T
MANE Select: NM_020180
Type: single nucleotide variant
Location: chr18:37321839 (GRCh38)
Gene constraint: LOEUF 0.546 · pLI 0.84 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 62.70 · 2 PDB
Residue 138: the 'sufficient for rna-binding and mse-dependent splicing activity' region; the 'disordered' region

Full CELF4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neurodevelopmental disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CELF4 p.Gly193Val Uncertain significance ★★ ⚠ same condition
CELF4 c.370-67640C>A Uncertain significance ★ same condition
CELF4 c.577+2T>G Uncertain significance ★ same condition
CELF4 p.Cys194Ter Uncertain significance ★ same condition
CELF4 p.Gln271Ter Uncertain significance ★ same condition
CELF4 p.Glu117Ter Uncertain significance ★ same condition
CELF4 p.Gly186Ala Uncertain significance ★ ⚠ same condition
CELF4 p.His116Gln 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/celf4-p-arg138ter (accessed [today's date]).

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