Is CELF4 p.Ala133= (c.399G>A) pathogenic?

CELF4 p.Ala133= (c.399G>A) is classified Likely benign in CELF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-06-01). Rare (popmax 0.349%, nfe).

How common is CELF4 p.Ala133= (c.399G>A) in the general population?

CELF4 p.Ala133= (c.399G>A) is rare (popmax 0.349%, nfe) (gnomAD).

CELF4 p.Ala133=

c.399G>A · VCV4681313

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.349%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.067	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -1.1, phastCons 1
Overall
CADD	16.19	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.349% European (non-Finnish) · 4,115/1,179,652 alleles

Filtering AF 0.34% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.336%

Overall 0.333% 5,369/1,613,424 alleles · rare exomes 4,919/1,461,078 · genomes 450/152,346 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.632%	158
Ashkenazi Jewishnot grpmax-eligible	0.578%	173
European (non-Finnish)grpmax	0.349%	287
Remaining individualsnot grpmax-eligible	0.293%	341
Admixed American	0.283%	353
South Asian	0.279%	358
Middle Eastern	0.116%	865
African / African-American	0.068%	1,472
East Asian	0.0312%	3,204

Finnish 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: CELF4
Protein: p.Ala133=
Coding: c.399G>A
MANE Select: NM_020180
Type: single nucleotide variant
Location: chr18:37321852 (GRCh38)
Gene constraint: LOEUF 0.546 · pLI 0.84 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 62.70 · 2 PDB
Residue 133: the rrm 1 domain; 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

Similar variants

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
CELF4 c.370-67640C>A Uncertain significance ★ same type
CELF4 c.577+2T>G 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-ala133 (accessed [today's date]).

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