# NM_001007553.3(CSDE1):c.2374del (p.Arg792fs)

https://sugi.bio/variant/csde1-p-arg792fs

## Summary

**CSDE1 p.Arg792fs (c.2374del)** is classified **Uncertain significance** in CSDE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-30). Very rare (popmax 0.00535%, afr).

**At a glance:** Uncertain significance · review: Single submitter · rsID rs1311412281 · 1 submitter · very rare (popmax 0.00535%, afr)

## For patients & families {#patients}

This is a change in the CSDE1 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 | [CSDE1](https://sugi.bio/atlas/gene/CSDE1/) |
| Protein change (HGVS p.) | p.Arg792fs |
| Coding change (HGVS c.) | c.2374del |
| MANE Select transcript | [NM_001007553](https://www.ncbi.nlm.nih.gov/nuccore/NM_001007553) |
| dbSNP | [rs1311412281](https://www.ncbi.nlm.nih.gov/snp/rs1311412281/) |
| Variant type | Deletion |
| Location | chr1:114718192-114718192 (GRCh38) |
| ClinVar | [VCV1697143](https://www.ncbi.nlm.nih.gov/clinvar/variation/1697143/) |

**All HGVS expressions:** `LRG_92:g.3703del`, `NC_000001.10:g.115260814del`, `NC_000001.11:g.114718193del`, `NG_007572.1:g.3703del`, `NM_001007553.3:c.2374del`, `NM_001130523.3:c.2419del`, `NM_001242891.2:c.2512del`, `NM_001242892.2:c.2374del`, `NM_001242893.2:c.2281del`, `NM_007158.6:c.2281del`

## 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 2.797, GERP 2.58, 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 0.295, pLI 1), supporting a loss-of-function disease mechanism. *Descriptive; not an applied PVS1 code.*
- Nonsense-mediated decay: the premature termination codon is **in the last exon (20 of 20)** — predicted to **escape NMD**, so the truncated protein is likely expressed. An input to PVS1, not an applied code.
- CADD: **PHRED 34.0**. No single ClinGen-calibrated threshold exists and the expert panels that use CADD disagree — GUCY2D/AIPL1 require ≥ 20.0 for an untranslated-region variant, ABCA4 ≥ 28.1 for a synonymous or indel variant, the Pulmonary Hypertension panel imports Pejaver 2022's missense-calibrated numbers, and the Antibody Deficiencies panel declines CADD entirely for PIK3CD. CADD v1.7 also incorporates Zoonomia phyloP, so it partly re-expresses the conservation above. *Descriptive; no threshold applied.*
- 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 (gnomAD v4.1): grpmax **0.00535%** (afr) · FAF95 0.00175% · FAF99 0.00104% · 4/74,780 in the highest group · 4/1,613,638 alleles overall — very rare (popmax 0.00535%, afr).

*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}

**CSDE1** population constraint: LOEUF 0.295, pLI 1, missense-Z 4.0667. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

Curated gene–disease validity (ClinGen):

- **complex neurodevelopmental disorder** — Definitive (AD)

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 80.05, 31% of residues very-high.

**5 experimental structure(s)** (PDB): [1WFQ](https://www.rcsb.org/structure/1WFQ), [1X65](https://www.rcsb.org/structure/1X65), [2YTV](https://www.rcsb.org/structure/2YTV), [2YTX](https://www.rcsb.org/structure/2YTX), [2YTY](https://www.rcsb.org/structure/2YTY).

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

*Describes the biological roles of CSDE1 (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:** CSDE1's established molecular role includes RNA binding.


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

**Molecular function:** RNA binding, RNA stem-loop binding, lncRNA binding, RISC complex binding.

**Biological process:** cytoplasmic stress granule assembly, positive regulation of translation, CRD-mediated mRNA stabilization, nuclear-transcribed mRNA catabolic process, no-go decay, IRES-dependent viral translational initiation, negative regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay.

## Clinical significance {#significance}

**Uncertain significance** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2022-08-30.

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

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| GeneDx | Uncertain significance | criteria provided, single submitter | clinical testing | 2022-08-30 |

**Reported phenotype names (ClinVar):** not provided, none provided.

## Similar variants {#similar}

Related CSDE1 variant pages (same residue, condition, or type): [CSDE1 p.Arg792Cys](/variant/csde1-p-arg792cys), [CSDE1 c.1-1710del](/variant/csde1-c-1-minus-1710del), [CSDE1 p.Asn689fs](/variant/csde1-p-asn689fs), [CSDE1 c.403-13_403-10del](/variant/csde1-c-403-minus-13-403-minus-10del), [CSDE1 c.838-19del](/variant/csde1-c-838-minus-19del), [CSDE1 c.310-11_310-10del](/variant/csde1-c-310-minus-11-310-minus-10del).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-06); 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 1697143). 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.*