Is CELF4 p.Ala294Thr (c.880G>A) pathogenic?

CELF4 p.Ala294Thr (c.880G>A) is classified Likely benign in CELF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-15). AlphaMissense: likely benign (0.1462); Ultra-rare (popmax 0.0187%, sas).

How common is CELF4 p.Ala294Thr (c.880G>A) in the general population?

CELF4 p.Ala294Thr (c.880G>A) is ultra-rare (popmax 0.0187%, sas) (gnomAD).

What do computational predictors say about CELF4 p.Ala294Thr (c.880G>A)?

AlphaMissense predicts likely benign (score 0.1462) — an in-silico prediction, not a clinical call.

CELF4 p.Ala294Thr

c.880G>A · rs765103903 · VCV2470443

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1462 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1462	likely benign
REVEL	0.369	indeterminate
SaProt	LLR -8.75	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 21 kb · p 4.4e-06 · regional, not allelic
Overall
CADD	33.0	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 0.0187% South Asian · 17/91,044 alleles

Filtering AF 0.0118% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00976%

Overall 0.00558% 90/1,613,020 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0187%	5,356
Finnishnot grpmax-eligible	0.011%	9,073
Remaining individualsnot grpmax-eligible	0.00641%	15,611
European (non-Finnish)	0.00517%	19,343
East Asian	0.00223%	44,890

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.Ala294Thr
Coding: c.880G>A
MANE Select: NM_020180
dbSNP: rs765103903
Type: single nucleotide variant
Location: chr18:37273085 (GRCh38)
Gene constraint: LOEUF 0.546 · pLI 0.84 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 62.70 · 2 PDB
Residue 294: 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.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-ala294thr (accessed [today's date]).

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