Is CELF1 p.Val153Ile (c.457G>A) pathogenic?

CELF1 p.Val153Ile (c.457G>A) is classified Uncertain significance in CELF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-08). AlphaMissense: likely benign (0.0714); Very rare (popmax 0.0022%, sas).

How common is CELF1 p.Val153Ile (c.457G>A) in the general population?

CELF1 p.Val153Ile (c.457G>A) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about CELF1 p.Val153Ile (c.457G>A)?

AlphaMissense predicts likely benign (score 0.0714) — an in-silico prediction, not a clinical call.

CELF1 p.Val153Ile

c.457G>A · VCV4651854

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0714 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0714	likely benign
REVEL	0.082	moderately benign-leaning
SaProt	LLR -6.35	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.23	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 7.7	GERP 2.6, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 27 kb · p 1.2e-24 · regional, not allelic
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V126I vs ClinVar V153I) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,024 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000137% 2/1,461,566 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: CELF1
Protein: p.Val153Ile
Coding: c.457G>A
MANE Select: NM_001376376
Type: single nucleotide variant
Location: chr11:47484458 (GRCh38)
Gene constraint: LOEUF 0.247 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.17 · 8 PDB
Residue 153: the rrm 2 domain; a β-strand

Full CELF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CELF1 p.Ser507= Benign ★★ same type
CELF1 c.606+2T>A Uncertain significance ★ same type
CELF1 p.Ala237Thr Uncertain significance ★ ⚠ same type
CELF1 p.Ala401Val Uncertain significance ★ ⚠ same type
CELF1 p.Ala99Val Uncertain significance ★ ⚠ same type
CELF1 p.Arg152Gln Uncertain significance ★ ⚠ same type
CELF1 p.Arg506His Uncertain significance ★ ⚠ same type
CELF1 p.Arg60Gln 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/celf1-p-val153ile (accessed [today's date]).

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