Is CELF5 p.Pro451Leu (c.1352C>T) pathogenic?

CELF5 p.Pro451Leu (c.1352C>T) is classified Uncertain significance in CELF5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). AlphaMissense: likely benign (0.155); Very rare (popmax 0.00267%, afr).

How common is CELF5 p.Pro451Leu (c.1352C>T) in the general population?

CELF5 p.Pro451Leu (c.1352C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about CELF5 p.Pro451Leu (c.1352C>T)?

AlphaMissense predicts likely benign (score 0.155) — an in-silico prediction, not a clinical call.

CELF5 p.Pro451Leu

c.1352C>T · VCV3490006

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.155 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.155	likely benign
REVEL	0.438	indeterminate
SaProt	LLR -13.03	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.46	unconstrained · MANE · 7,433 bp · p 7.7e-10 · regional, not allelic
Overall
CADD	27.2	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 0.00267% African / African-American · 2/74,942 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000929% 15/1,614,042 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,471
South Asian	0.0011%	91,092
European (non-Finnish)	0.00102%	98,333

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: CELF5
Protein: p.Pro451Leu
Coding: c.1352C>T
MANE Select: NM_021938
Type: single nucleotide variant
Location: chr19:3293340 (GRCh38)
Gene constraint: LOEUF 0.248 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.74 · 1 PDB
Residue 451: the rrm 3 domain

Full CELF5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CELF5 p.Gln364Pro Uncertain significance ★★ ⚠ same type
CELF5 p.Ala309Thr Uncertain significance ★ ⚠ same type
CELF5 p.Ala373Val Uncertain significance ★ ⚠ same type
CELF5 p.Arg117Trp Uncertain significance ★ ⚠ same type
CELF5 p.Arg129His Uncertain significance ★ ⚠ same type
CELF5 p.Arg218Leu Uncertain significance ★ ⚠ same type
CELF5 p.Gln12Arg Uncertain significance ★ ⚠ same type
CELF5 p.Gln13Leu 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/celf5-p-pro451leu (accessed [today's date]).

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