Is CELF1 p.Ile119Val (c.355A>G) pathogenic?

CELF1 p.Ile119Val (c.355A>G) is classified Uncertain significance in CELF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-20). AlphaMissense: likely benign (0.1301); Very rare (popmax 0.00986%, nfe).

How common is CELF1 p.Ile119Val (c.355A>G) in the general population?

CELF1 p.Ile119Val (c.355A>G) is very rare (popmax 0.00986%, nfe) (gnomAD).

What do computational predictors say about CELF1 p.Ile119Val (c.355A>G)?

AlphaMissense predicts likely benign (score 0.1301) — an in-silico prediction, not a clinical call.

CELF1 p.Ile119Val

c.355A>G · rs747689679 · VCV2409251

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1301 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00986%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1301	likely benign
REVEL	0.195	benign-leaning
SaProt	LLR -9.45	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.6, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 27 kb · p 1.2e-24 · regional, not allelic
Overall
CADD	24.9	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 I92V vs ClinVar I119V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00986% European (non-Finnish) · 116/1,176,908 alleles

Filtering AF 0.00836% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00778%

Overall 0.00733% 118/1,610,612 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00986%	10,146
Remaining individualsnot grpmax-eligible	0.00321%	31,188

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.Ile119Val
Coding: c.355A>G
MANE Select: NM_001376376
dbSNP: rs747689679
Type: single nucleotide variant
Location: chr11:47486786 (GRCh38)
Gene constraint: LOEUF 0.247 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.17 · 8 PDB
Residue 119: the rrm 2 domain

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

Similar variants

CELF1 p.Ile119Met Uncertain significance ★ ⚠ same residue
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

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-ile119val (accessed [today's date]).

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