Is CELF2 p.Ala4Val (c.11C>T) pathogenic?

CELF2 p.Ala4Val (c.11C>T) is classified Uncertain significance in CELF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-02). Very rare (popmax 0.000983%, nfe).

How common is CELF2 p.Ala4Val (c.11C>T) in the general population?

CELF2 p.Ala4Val (c.11C>T) is very rare (popmax 0.000983%, nfe) (gnomAD).

CELF2 p.Ala4Val

c.11C>T · VCV4812929

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000983%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.135	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7	GERP 0.95, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 147 kb · p 0.41 · regional, not allelic
Overall
CADD	25.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000983% European (non-Finnish) · 11/1,119,436 alleles

Filtering AF 0.000527% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000385%

Overall 0.000889% 12/1,349,990 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00388%	25,772
European (non-Finnish)grpmax	0.000983%	101,767

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CELF2
Protein: p.Ala4Val
Coding: c.11C>T
MANE Select: NM_001326342
Type: single nucleotide variant
Location: chr10:11018100 (GRCh38)
Gene constraint: LOEUF 0.294 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.26 · 7 PDB
Residue 4: 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.Leu4Val Likely benign same residue
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.Val95Leu Uncertain significance ★★ ⚠ same type
CELF2 p.Arg506His Pathogenic ★ same type
CELF2 p.Arg506Leu Pathogenic ★ 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-ala4val (accessed [today's date]).

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