# NM_001256447.2(BCAP31):c.733_736del (p.Glu245fs)

https://sugi.bio/variant/bcap31-p-glu245fs

## Summary

**BCAP31 p.Glu245fs (c.733_736del)** is classified **Uncertain significance** in BCAP31 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-10-01). No gnomAD frequency available for this variant.

**At a glance:** Uncertain significance · review: Single submitter · rsID rs1603221175 · 1 submitter · no gnomAD frequency available for this variant

## For patients & families {#patients}

This is a change in the BCAP31 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 | [BCAP31](https://sugi.bio/atlas/gene/BCAP31/) |
| Protein change (HGVS p.) | p.Glu245fs |
| Coding change (HGVS c.) | c.733_736del |
| MANE Select transcript | [NM_001256447](https://www.ncbi.nlm.nih.gov/nuccore/NM_001256447) |
| dbSNP | [rs1603221175](https://www.ncbi.nlm.nih.gov/snp/rs1603221175/) |
| Variant type | Microsatellite |
| Location | chrX:153700942-153700945 (GRCh38) |
| ClinVar | [VCV807839](https://www.ncbi.nlm.nih.gov/clinvar/variation/807839/) |

**All HGVS expressions:** `NC_000023.10:g.152966397CTTC[1]`, `NC_000023.11:g.153700942CTTC[1]`, `NG_023231.1:g.28798GAAG[1]`, `NM_001139441.1:c.733_736del`, `NM_001139457.2:c.934_937del`, `NM_001256447.2:c.733_736del`, `NM_005745.8:c.733_736del`

## 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 5.786, GERP -0.856, phastCons 1 — highly conserved position (PP3-type support)
- Molecular consequence: **frameshift** — a predicted loss-of-function variant. ClinGen curates **sufficient evidence for haploinsufficiency** in this gene, 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 (8 of 8)** — predicted to **escape NMD**, so the truncated protein is likely expressed. An input to PVS1, not an applied code.
- 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.
- Repeat context: **segmental_duplication** (chr16:33973779, chr16:32861288). Short reads may not map uniquely here, so both the call and its population frequency are less reliable. *A qualifier on how reliably this variant can be called and counted — not a pathogenicity signal.*
- 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}

**BCAP31** population constraint: ClinGen dosage — haploinsufficiency 3, triplosensitivity 0 (0–3 scale). *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):

- **severe motor and intellectual disabilities-sensorineural deafness-dystonia syndrome** — Definitive (XL)

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 84.74, 51% of residues very-high.

**3 experimental structure(s)** (PDB): [4JZL](https://www.rcsb.org/structure/4JZL), [4JZP](https://www.rcsb.org/structure/4JZP), [8XWX](https://www.rcsb.org/structure/8XWX).

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

*Describes the biological roles of BCAP31 (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:** BCAP31 participates in disease-associated pathways. In Reactome, BCAP31 is annotated in disease pathway(s) including **RSV-host interactions**.

**Disease mechanism (Reactome):** BCAP31 loss or alteration is curated in [RSV-host interactions](https://reactome.org/content/detail/R-HSA-9833110).

### Pathways affected {#pathways}

BCAP31 participates in **5 Reactome pathways** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| ⚕ [RSV-host interactions](https://reactome.org/content/detail/R-HSA-9833110) | curated |
| [Antigen Presentation: Folding, assembly and peptide loading of class I MHC](https://reactome.org/content/detail/R-HSA-983170) | curated |
| [Apoptotic cleavage of cellular proteins](https://reactome.org/content/detail/R-HSA-111465) | curated |
| [Apoptotic execution phase](https://reactome.org/content/detail/R-HSA-75153) | curated |
| [RHOA GTPase cycle](https://reactome.org/content/detail/R-HSA-8980692) | curated |

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

**Biological process:** obsolete protein targeting to mitochondrion, response to endoplasmic reticulum stress, positive regulation of retrograde protein transport, ER to cytosol, positive regulation of ERAD pathway, positive regulation of ubiquitin-dependent protein catabolic process, positive regulation of intrinsic apoptotic signaling pathway.

## Clinical significance {#significance}

**Uncertain significance** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2018-10-01.

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

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| CeGaT Center for Human Genetics Tuebingen | Uncertain significance | criteria provided, single submitter | clinical testing | 2018-10-01 |

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

## Similar variants {#similar}

Related BCAP31 variant pages (same residue, condition, or type): [BCAP31 p.Glu245Lys](/variant/bcap31-p-glu245lys), [BCAP31 p.Leu122fs](/variant/bcap31-p-leu122fs), [BCAP31 p.Tyr104fs](/variant/bcap31-p-tyr104fs), [BCAP31 p.Asp75del](/variant/bcap31-p-asp75del), [BCAP31 p.Phe52del](/variant/bcap31-p-phe52del), [BCAP31 c.478-276GCCAGGG[2]](/variant/bcap31-c-478-minus-276gccaggg-2).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-11); 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 2026-07-14); 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 807839). 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.*