# NM_022101.4(STEEP1):c.163del (p.Arg55fs)

https://sugi.bio/variant/steep1-p-arg55fs

## Summary

**STEEP1 p.Arg55fs (c.163del)** is classified **Likely pathogenic** in STEEP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-23). No gnomAD frequency available for this variant; Associated with intellectual disability, X-linked 107.

**At a glance:** Likely pathogenic · review: Single submitter · rsID rs2147360775 · 1 submitter · 1 linked condition · no gnomAD frequency available for this variant

## For patients & families {#patients}

This is a change in the STEEP1 gene that is considered likely disease-causing, submitted by 1 submitter, and is linked to intellectual disability, X-linked 107.

*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:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0022698/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [STEEP1](https://sugi.bio/atlas/gene/STEEP1/) |
| Protein change (HGVS p.) | p.Arg55fs |
| Coding change (HGVS c.) | c.163del |
| MANE Select transcript | [NM_022101](https://www.ncbi.nlm.nih.gov/nuccore/NM_022101) |
| dbSNP | [rs2147360775](https://www.ncbi.nlm.nih.gov/snp/rs2147360775/) |
| Variant type | Deletion |
| Location | chrX:119560347-119560347 (GRCh38) |
| ClinVar | [VCV1698675](https://www.ncbi.nlm.nih.gov/clinvar/variation/1698675/) |

**All HGVS expressions:** `NC_000023.10:g.118694311del`, `NC_000023.11:g.119560348del`, `NG_016378.1:g.10088del`, `NM_001170569.1:c.16del`, `NM_001170570.2:c.163del`, `NM_022101.4:c.163del`

## Computational & population evidence {#evidence}

**Concordance:** 1 independent predictor **concordant** with the ClinVar classification.

- **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 5.913, GERP 1.94, phastCons 1 — highly conserved position (PP3-type support)
- Molecular consequence: **frameshift** — a predicted loss-of-function variant. *Descriptive; not an applied PVS1 code.*
- Nonsense-mediated decay: the premature termination codon is **in exon 2 of 7**, 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}


Curated gene–disease validity (ClinGen):

- **intellectual disability, X-linked 107** — Moderate (XL)

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 76.15, 37% of residues very-high.

**2 experimental structure(s)** (PDB): [8C6J](https://www.rcsb.org/structure/8C6J), [9FMD](https://www.rcsb.org/structure/9FMD).

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

*Describes the biological roles of STEEP1 (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:** STEEP1's established molecular role includes protein-macromolecule adaptor activity.


### Pathways affected {#pathways}

STEEP1 participates in **1 Reactome pathway** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [mRNA Splicing - Major Pathway](https://reactome.org/content/detail/R-HSA-72163) | curated |

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

**Molecular function:** protein-macromolecule adaptor activity.

**Biological process:** endoplasmic reticulum to Golgi vesicle-mediated transport, obsolete protein exit from endoplasmic reticulum, endoplasmic reticulum membrane organization.

## Clinical significance {#significance}

**Likely pathogenic** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2022-05-23.

**Submitter consensus:** unanimous (1/1 Likely pathogenic).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Likely pathogenic | criteria provided, single submitter | clinical testing | 2022-05-23 |

## Associated conditions {#conditions}

[intellectual disability, X-linked 107](https://sugi.bio/atlas/disease/intellectual-disability-x-linked-107/).

**Reported phenotype names (ClinVar):** Intellectual disability, X-linked 107, INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED 107, MENTAL RETARDATION, X-LINKED 107.

## Similar variants {#similar}

Related STEEP1 variant pages (same residue, condition, or type): [STEEP1 p.Leu27fs](/variant/steep1-p-leu27fs), [STEEP1 p.Arg55Gln](/variant/steep1-p-arg55gln), [STEEP1 p.Met77fs](/variant/steep1-p-met77fs), [STEEP1 p.Arg55Trp](/variant/steep1-p-arg55trp), [STEEP1 c.-2T>C](/variant/steep1-c-minus-2t-c), [STEEP1 p.Gly125=](/variant/steep1-p-gly125), [STEEP1 p.Glu167_Glu168del](/variant/steep1-p-glu167-glu168del), [STEEP1 p.Arg15Leu](/variant/steep1-p-arg15leu).

### 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 1698675). 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.*