# NM_014014.5(SNRNP200):c.4986CAT[1] (p.Ile1663del)

https://sugi.bio/variant/snrnp200-p-ile1663del

## Summary

**SNRNP200 p.Ile1663del (c.4986CAT[1])** is classified **Uncertain significance** in SNRNP200 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-06). Very rare (popmax 0.000169%, nfe).

**At a glance:** Uncertain significance · review: Single submitter · rsID rs1434410149 · 1 submitter · very rare (popmax 0.000169%, nfe)

## For patients & families {#patients}

This is a change in the SNRNP200 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 | [SNRNP200](https://sugi.bio/atlas/gene/SNRNP200/) |
| Protein change (HGVS p.) | p.Ile1663del |
| Coding change (HGVS c.) | c.4986CAT[1] |
| MANE Select transcript | [NM_014014](https://www.ncbi.nlm.nih.gov/nuccore/NM_014014) |
| dbSNP | [rs1434410149](https://www.ncbi.nlm.nih.gov/snp/rs1434410149/) |
| Variant type | Microsatellite |
| Location | chr2:96281847-96281849 (GRCh38) |
| ClinVar | [VCV2002516](https://www.ncbi.nlm.nih.gov/clinvar/variation/2002516/) |

**All HGVS expressions:** `NC_000002.11:g.96947587GAT[1]`, `NC_000002.12:g.96281849GAT[1]`, `NG_016973.1:g.28708CAT[1]`, `NM_014014.5:c.4986CAT[1]`

## 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 7.629, GERP 1.91, phastCons 1 — highly conserved position (PP3-type support)
- Molecular consequence: **in-frame indel**.
- SpliceAI: **not assessed** — the release is built from a substitutions-only source, so it holds no microsatellite 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 **0.000169%** (nfe) · FAF95 2.8e-05% · FAF99 1.1e-05% · 2/1,179,958 in the highest group · 3/1,614,070 alleles overall — very rare (popmax 0.000169%, nfe).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| Remaining individuals (not grpmax-eligible) | 0.0016% | 62,498 |
| European (non-Finnish) (grpmax) | 0.000169% | 589,977 |

Remaining individuals shows a higher raw frequency than the grpmax group. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and "Remaining individuals" — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

*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}

**SNRNP200** population constraint: LOEUF 0.312, pLI 1, missense-Z 8.766. *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):

- **SNRNP200-related dominant retinopathy** — Definitive (AD)

## Protein context {#protein}

Residue **1663** lies in a β-strand; the helicase c-terminal 2 domain; the 'interaction with c9orf78 and wbp4' region; the 'interaction with tssc4' region.

AlphaFold model confidence (whole protein): pLDDT 82.89, 45% of residues very-high.

**85 experimental structure(s)** (PDB): [2Q0Z](https://www.rcsb.org/structure/2Q0Z), [3JCR](https://www.rcsb.org/structure/3JCR), [4F91](https://www.rcsb.org/structure/4F91), [4F92](https://www.rcsb.org/structure/4F92), [4F93](https://www.rcsb.org/structure/4F93), [4KIT](https://www.rcsb.org/structure/4KIT) — incl. mutant structure 8CH6.

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

*Describes the biological roles of SNRNP200 (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:** SNRNP200's established molecular role includes RNA binding. p.Ile1663del falls in the helicase c-terminal 2 domain. In Reactome, SNRNP200 is annotated in disease pathway(s) including **Dengue Virus-Host Interactions**.

**Disease mechanism (Reactome):** SNRNP200 loss or alteration is curated in [Dengue Virus-Host Interactions](https://reactome.org/content/detail/R-HSA-9918481).

### Pathways affected {#pathways}

SNRNP200 participates in **3 Reactome pathways** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| ⚕ [Dengue Virus-Host Interactions](https://reactome.org/content/detail/R-HSA-9918481) | curated |
| [mRNA Splicing - Major Pathway](https://reactome.org/content/detail/R-HSA-72163) | curated |
| [mRNA Splicing - Minor Pathway](https://reactome.org/content/detail/R-HSA-72165) | curated |

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

**Molecular function:** RNA binding, RNA helicase activity, helicase activity, identical protein binding.

**Biological process:** spliceosome conformational change to release U4 (or U4atac) and U1 (or U11), mRNA splicing, via spliceosome, osteoblast differentiation.

## Clinical significance {#significance}

**Uncertain significance** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2022-06-06.

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

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Labcorp Genetics (formerly Invitae), Labcorp | Uncertain significance | criteria provided, single submitter | clinical testing | 2022-06-06 |

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

## Similar variants {#similar}

Related SNRNP200 variant pages (same residue, condition, or type): [SNRNP200 p.Ile1663Val](/variant/snrnp200-p-ile1663val), [SNRNP200 p.Ile1663Thr](/variant/snrnp200-p-ile1663thr), [SNRNP200 c.1376_1377+1del](/variant/snrnp200-c-1376-1377-plus-1del), [SNRNP200 c.5324-12_5324-11del](/variant/snrnp200-c-5324-minus-12-5324-minus-11del), [SNRNP200 p.Asp942del](/variant/snrnp200-p-asp942del), [SNRNP200 p.Glu579del](/variant/snrnp200-p-glu579del), [SNRNP200 p.His573del](/variant/snrnp200-p-his573del), [SNRNP200 p.Lys256del](/variant/snrnp200-p-lys256del).

### 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 2002516). 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.*