Is CELF4 p.Leu159Val (c.475C>G) pathogenic?

CELF4 p.Leu159Val (c.475C>G) is classified Uncertain significance in CELF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-24). AlphaMissense: likely pathogenic (0.8764); Absent from gnomAD v4.1; Associated with neurodevelopmental disorder.

What condition is associated with CELF4 p.Leu159Val (c.475C>G)?

CELF4 p.Leu159Val (c.475C>G) is associated with neurodevelopmental disorder (ClinVar).

How common is CELF4 p.Leu159Val (c.475C>G) in the general population?

CELF4 p.Leu159Val (c.475C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CELF4 p.Leu159Val (c.475C>G)?

AlphaMissense predicts likely pathogenic (score 0.8764) — an in-silico prediction, not a clinical call.

CELF4 p.Leu159Val

c.475C>G · VCV3362799

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8764 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neurodevelopmental disorder

Computational evidence

Protein change
AlphaMissense	0.8764	likely pathogenic
REVEL	0.215	benign-leaning
SaProt	LLR -9.97	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.2, phastCons 1
Regional constraint	o/e 0.05	constrained · MANE · 47 kb · p 4.5e-05 · regional, not allelic
Overall
CADD	26.9	PHRED · no single calibrated threshold — expert panels disagree

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

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.Leu159Val
Coding: c.475C>G
MANE Select: NM_020180
Type: single nucleotide variant
Location: chr18:37275217 (GRCh38)
Gene constraint: LOEUF 0.546 · pLI 0.84 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 62.70 · 2 PDB
Residue 159: the rrm 2 domain; the 'sufficient for rna-binding and mse-dependent splicing activity' 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.Arg138Ter 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

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-leu159val (accessed [today's date]).

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