Is CELF2 p.Leu17Ser (c.50T>C) pathogenic?

CELF2 p.Leu17Ser (c.50T>C) is classified Likely benign in CELF2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-05-06). AlphaMissense: likely benign (0.0842); Ultra-rare (popmax 0.0446%, nfe); Associated with CELF2-related disorder.

What condition is associated with CELF2 p.Leu17Ser (c.50T>C)?

CELF2 p.Leu17Ser (c.50T>C) is associated with CELF2-related disorder (ClinVar).

How common is CELF2 p.Leu17Ser (c.50T>C) in the general population?

CELF2 p.Leu17Ser (c.50T>C) is ultra-rare (popmax 0.0446%, nfe) (gnomAD).

What do computational predictors say about CELF2 p.Leu17Ser (c.50T>C)?

AlphaMissense predicts likely benign (score 0.0842) — an in-silico prediction, not a clinical call.

CELF2 p.Leu17Ser

c.50T>C · rs200779130 · VCV3048917

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0842 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0446%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

CELF2-related disorder

Computational evidence

Protein change
AlphaMissense	0.0842	likely benign
REVEL	0.353	indeterminate
SaProt	LLR -6.45	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2, phastCons 1
Overall
CADD	23.3	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 0.0446% European (non-Finnish) · 526/1,179,836 alleles

Filtering AF 0.0414% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0401%

Overall 0.0366% 591/1,613,816 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0446%	2,243
South Asian	0.0373%	2,679
Remaining individualsnot grpmax-eligible	0.024%	4,164
Admixed American	0.01%	10,000
African / African-American	0.00801%	12,484
Finnishnot grpmax-eligible	0.00625%	16,007

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: CELF2
Protein: p.Leu17Ser
Coding: c.50T>C
MANE Select: NM_001326342 · reported on NM_001326331
dbSNP: rs200779130
Type: single nucleotide variant
Location: chr10:11005437 (GRCh38)
Gene constraint: LOEUF 0.294 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.26 · 7 PDB
Residue 17: the 'necessary for rna-binding, tnnt2 exon 5 and nmda r1 exon 21 inclusion' region

Full CELF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CELF2-related disorder

Similar variants

CELF2 p.Met1Lys Uncertain significance ★ same condition
CELF2 c.977-2A>T Likely pathogenic same condition
CELF2 c.976+4A>T Uncertain significance same condition
CELF2 c.1097-6G>T Likely benign same condition
CELF2 c.16+5G>A Likely benign same condition
CELF2 p.Leu4Val Likely benign same condition
CELF2 p.Arg506Cys Pathogenic/Likely pathogenic ★★ same type
CELF2 p.Arg513His Likely pathogenic ★★ 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/celf2-p-leu17ser (accessed [today's date]).

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