# NM_001326342.2(CELF2):c.1316_1317del (p.Phe439fs)

https://sugi.bio/variant/celf2-p-phe439fs

## Summary

**CELF2 p.Phe439fs (c.1316_1317del)** is classified **Uncertain significance** in CELF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-16). No gnomAD frequency available for this variant.

**At a glance:** Uncertain significance · review: Single submitter · rsID rs2549996551 · 1 submitter · no gnomAD frequency available for this variant

## For patients & families {#patients}

This is a change in the CELF2 gene that is currently of uncertain significance — a definitive interpretation has not yet been established, submitted by 1 submitter.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

**Support & next steps:** [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [CELF2](https://sugi.bio/atlas/gene/CELF2/) |
| Protein change (HGVS p.) | p.Phe439fs |
| Coding change (HGVS c.) | c.1316_1317del |
| MANE Select transcript | [NM_001326342](https://www.ncbi.nlm.nih.gov/nuccore/NM_001326342) |
| dbSNP | [rs2549996551](https://www.ncbi.nlm.nih.gov/snp/rs2549996551/) |
| Variant type | Deletion |
| Location | chr10:11325856-11325857 (GRCh38) |
| ClinVar | [VCV2576878](https://www.ncbi.nlm.nih.gov/clinvar/variation/2576878/) |

**All HGVS expressions:** `NC_000010.10:g.11367820_11367821del`, `NC_000010.11:g.11325857_11325858del`, `NM_001025076.2:c.1223_1224del`, `NM_001025077.3:c.1277_1278del`, `NM_001083591.1:c.1217_1218del`, `NM_001326317.2:c.1205_1206del`, `NM_001326318.2:c.1223_1224del`, `NM_001326319.2:c.1277_1278del`, `NM_001326320.2:c.1223_1224del`, `NM_001326321.2:c.1247_1248del`, `NM_001326323.2:c.1265_1266del`, `NM_001326324.2:c.1223_1224del`, `NM_001326325.2:c.1370_1371del`, `NM_001326326.2:c.1313_1314del`, `NM_001326327.2:c.1331_1332del`, `NM_001326328.2:c.1223_1224del`, `NM_001326329.2:c.1205_1206del`, `NM_001326330.2:c.1223_1224del`, `NM_001326331.2:c.1295_1296del`, `NM_001326332.2:c.1277_1278del`, `NM_001326333.2:c.611_612del`, `NM_001326334.2:c.1223_1224del`, `NM_001326335.2:c.1289_1290del`, `NM_001326336.2:c.1349_1350del`, `NM_001326337.2:c.1109_1110del`, `NM_001326338.2:c.944_945del`, `NM_001326339.2:c.962_963del`, `NM_001326340.2:c.1352_1353del`, `NM_001326341.2:c.1298_1299del`, `NM_001326342.2:c.1316_1317del`, `NM_001326343.2:c.1370_1371del`, `NM_001326344.2:c.1205_1206del`, `NM_001326345.2:c.1223_1224del`, `NM_001326346.2:c.593_594del`, `NM_001326347.1:c.1241_1242del`, `NM_001326348.2:c.1205_1206del`, `NM_001326349.2:c.1223_1224del`, `NM_001394502.1:c.1295_1296del`, `NM_001394513.1:c.1298_1299del`, `NM_001394517.1:c.1205_1206del`, `NM_001394518.1:c.1310_1311del`, `NM_001394519.1:c.1310_1311del`, `NM_006561.4:c.1316_1317del`

## Computational & population evidence {#evidence}

**Concordance:** Mixed / partial computational evidence (see below).

- **Missense predictors (AlphaMissense/REVEL/SaProt) do not apply** to this variant type — they score amino-acid substitutions only. For non-missense variants the computational signal comes from conservation (below), not from a missing predictor score.
- Conservation: phyloP 6.012, GERP 0.662, phastCons 1 — highly conserved position (PP3-type support)
- Molecular consequence: **frameshift** — a predicted loss-of-function variant. the gene is **loss-of-function-intolerant** (LOEUF 0.294, pLI 1), supporting a loss-of-function disease mechanism. *Descriptive; not an applied PVS1 code.*
- Nonsense-mediated decay: the premature termination codon is **in exon 12 of 13**, so the transcript is predicted to undergo NMD.
- SpliceAI: **not assessed** — the release is built from a substitutions-only source, so it holds no deletion variants. That is a property of the dataset, not of the variant, and is not evidence against a splicing effect.
- Population frequency: **no gnomAD frequency available for this variant** — rarity (ACMG PM2) and BA1/BS1 cannot be assessed for this variant.

*Computational predictors are not independent (ClinGen Variant Classification guidance): AlphaMissense (Cheng et al. 2023) carries the ACMG weight for missense and conservation (phyloP/GERP/phastCons) for non-missense; REVEL (Pejaver-2022 calibrated strength bands) and SaProt (Su et al. 2023, structure-aware, ClinVar-independent protein language model, raw LLR) are shown as orthogonal agreement signals, not additive. For frequency, the gnomAD v4.1 grpmax filtering allele frequency (FAF95) is ClinGen's designated BA1/BS1 input (gnomAD v4 guidance v3.0, June 2025); BA1/BS1 thresholds are disease-specific, not a blanket 5%. Predictions, not a clinical determination.*

## Gene constraint & dosage {#gene-context}

**CELF2** population constraint: LOEUF 0.294, pLI 1, missense-Z 4.1462. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

## Protein context {#protein}

Residue **439** lies in the rrm 3 domain; an α-helix; the 'necessary for rna-binding, tnnt2 exon 5 and nmda r1 exon 21 inclusion' region.

AlphaFold model confidence (whole protein): pLDDT 66.26, 17% of residues very-high.

**7 experimental structure(s)** (PDB): [2MY7](https://www.rcsb.org/structure/2MY7), [2MY8](https://www.rcsb.org/structure/2MY8), [4LJM](https://www.rcsb.org/structure/4LJM), [4LMZ](https://www.rcsb.org/structure/4LMZ), [4TLQ](https://www.rcsb.org/structure/4TLQ), [5M8I](https://www.rcsb.org/structure/5M8I).

## What this gene does {#gene-function}

*Describes the biological roles of CELF2 (the gene this variant disrupts) — not effects measured for this specific variant. A damaging variant is expected to affect these functions and pathways; the degree depends on the variant.*

**How this variant is thought to act:** CELF2's established molecular role includes RNA binding. p.Phe439fs falls in the rrm 3 domain.


### Molecular function & processes (GO — experimentally supported) {#go}

**Molecular function:** RNA binding, pre-mRNA binding.

**Biological process:** mRNA splice site recognition.

## Clinical significance {#significance}

**Uncertain significance** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2023-02-16.

**Submitter consensus:** unanimous (1/1 Uncertain significance).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| GeneDx | Uncertain significance | criteria provided, single submitter | clinical testing | 2023-02-16 |

**Reported phenotype names (ClinVar):** not provided, none provided, RECLASSIFIED - ADRA2C POLYMORPHISM, RECLASSIFIED - ADRB1 POLYMORPHISM.

## Similar variants {#similar}

Related CELF2 variant pages (same residue, condition, or type): [CELF2 c.355-6858_403+3281del](/variant/celf2-c-355-minus-6858-403-plus-3281del), [CELF2 p.Ala295fs](/variant/celf2-p-ala295fs), [CELF2 p.Asp451fs](/variant/celf2-p-asp451fs), [CELF2 p.Lys466fs](/variant/celf2-p-lys466fs), [CELF2 p.Lys471fs](/variant/celf2-p-lys471fs), [CELF2 p.Met13fs](/variant/celf2-p-met13fs), [CELF2 c.355-48_403+52del](/variant/celf2-c-355-minus-48-403-plus-52del), [CELF2 p.Ala363_Leu364insTer](/variant/celf2-p-ala363-leu364inster).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-15); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-10-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 2576878). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*