Is CELF6 p.Leu240Val (c.718C>G) pathogenic?

CELF6 p.Leu240Val (c.718C>G) is classified Uncertain significance in CELF6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-01). AlphaMissense: likely benign (0.0771); Very rare (popmax 8.82e-05%, nfe).

How common is CELF6 p.Leu240Val (c.718C>G) in the general population?

CELF6 p.Leu240Val (c.718C>G) is very rare (popmax 8.82e-05%, nfe) (gnomAD).

What do computational predictors say about CELF6 p.Leu240Val (c.718C>G)?

AlphaMissense predicts likely benign (score 0.0771) — an in-silico prediction, not a clinical call.

CELF6 p.Leu240Val

c.718C>G · VCV4000135

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0771 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.82e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0771	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -8.57	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.45	donor gain · deltas
Constraint at this position
Conservation	phyloP 5	GERP -3.3, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 2,721 bp · p 0.007 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.82e-05% European (non-Finnish) · 1/1,134,256 alleles

Overall 7.41e-05% 1/1,349,290 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CELF6
Protein: p.Leu240Val
Coding: c.718C>G
MANE Select: NM_052840
Type: single nucleotide variant
Location: chr15:72289656 (GRCh38)
Gene constraint: LOEUF 1.082 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.19 · 1 PDB

Full CELF6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CELF6 p.Met40Thr Benign ★★ ⚠ same type
CELF6 p.Ala189Glu Uncertain significance ★ ⚠ same type
CELF6 p.Ala255Glu Uncertain significance ★ ⚠ same type
CELF6 p.Ala295Thr Uncertain significance ★ ⚠ same type
CELF6 p.Ala344Asp Uncertain significance ★ ⚠ same type
CELF6 p.Ala358Thr Uncertain significance ★ ⚠ same type
CELF6 p.Ala364Pro Uncertain significance ★ ⚠ same type
CELF6 p.Ala96Ser 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/celf6-p-leu240val (accessed [today's date]).

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