Is CELF4 p.Ala211Glu (c.632C>A) pathogenic?

CELF4 p.Ala211Glu (c.632C>A) is classified Uncertain significance in CELF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-12). AlphaMissense: likely pathogenic (0.7263); Very rare (popmax 0.00224%, eas).

How common is CELF4 p.Ala211Glu (c.632C>A) in the general population?

CELF4 p.Ala211Glu (c.632C>A) is very rare (popmax 0.00224%, eas) (gnomAD).

What do computational predictors say about CELF4 p.Ala211Glu (c.632C>A)?

AlphaMissense predicts likely pathogenic (score 0.7263) — an in-silico prediction, not a clinical call.

CELF4 p.Ala211Glu

c.632C>A · VCV4651865

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7263 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7263	likely pathogenic
REVEL	0.157	moderately benign-leaning
SaProt	LLR -14.61	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.2, phastCons 1
Regional constraint	o/e 0.61	unconstrained · MANE · 765 bp · p 0.00017 · regional, not allelic
Overall
CADD	28.9	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

Grpmax group 0.00224% East Asian · 1/44,648 alleles

Overall 0.000137% 2/1,454,702 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00224%	44,648
European (non-Finnish)	8.49e-05%	1,177,831

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: CELF4
Protein: p.Ala211Glu
Coding: c.632C>A
MANE Select: NM_020180
Type: single nucleotide variant
Location: chr18:37274830 (GRCh38)
Gene constraint: LOEUF 0.546 · pLI 0.84 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 62.70 · 2 PDB
Residue 211: the rrm 2 domain; an α-helix; 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

Similar variants

CELF4 p.Ala211Gly Uncertain significance ★ ⚠ same residue
CELF4 p.Ala211Thr Uncertain significance ★ ⚠ same residue
CELF4 p.Gly193Val Uncertain significance ★★ ⚠ same type
CELF4 p.Ala381= Benign/Likely benign ★★ same type
CELF4 p.Pro127= Benign ★★ same type
CELF4 p.Pro406= Benign ★★ same type
CELF4 p.Glu76Ter Pathogenic ★ same type
CELF4 c.1165+2T>C 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/celf4-p-ala211glu (accessed [today's date]).

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