Is CELF3 p.Phe194Tyr (c.581T>A) pathogenic?

CELF3 p.Phe194Tyr (c.581T>A) is classified Uncertain significance in CELF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-11). AlphaMissense: ambiguous (0.4412); Very rare (popmax 0.00667%, amr).

How common is CELF3 p.Phe194Tyr (c.581T>A) in the general population?

CELF3 p.Phe194Tyr (c.581T>A) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about CELF3 p.Phe194Tyr (c.581T>A)?

AlphaMissense predicts ambiguous (score 0.4412) — an in-silico prediction, not a clinical call.

CELF3 p.Phe194Tyr

c.581T>A · VCV4651861

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4412 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Computational evidence

Protein change
AlphaMissense	0.4412	ambiguous
REVEL	0.541	indeterminate
SaProt	LLR -9.82	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 2.1, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 8,731 bp · p 6.5e-15 · regional, not allelic
Overall
CADD	24.9	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 0.00667% Admixed American · 4/59,998 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000274% 4/1,461,646 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: CELF3
Protein: p.Phe194Tyr
Coding: c.581T>A
MANE Select: NM_007185
Type: single nucleotide variant
Location: chr1:151707841 (GRCh38)
Gene constraint: LOEUF 0.662 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.04 · 1 PDB

Full CELF3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CELF3 p.Ala146Thr Uncertain significance ★ ⚠ same type
CELF3 p.Ala206Ser Uncertain significance ★ ⚠ same type
CELF3 p.Ala206Thr Uncertain significance ★ ⚠ same type
CELF3 p.Ala216Glu Uncertain significance ★ ⚠ same type
CELF3 p.Ala221Thr Uncertain significance ★ ⚠ same type
CELF3 p.Ala276Thr Uncertain significance ★ ⚠ same type
CELF3 p.Ala312Val Uncertain significance ★ ⚠ same type
CELF3 p.Ala323Thr 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/celf3-p-phe194tyr (accessed [today's date]).

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