# NM_182641.4(BPTF):c.5564del (p.Pro1855fs)

https://sugi.bio/variant/bptf-p-pro1855fs

## Summary

**BPTF p.Pro1855fs (c.5564del)** is classified **Likely pathogenic** in BPTF (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-05-27). No gnomAD frequency available for this variant; Associated with neurodevelopmental disorder with dysmorphic facies and distal limb anomalies.

**At a glance:** Likely pathogenic · review: No assertion criteria · rsID rs2147246788 · 1 submitter · 1 linked condition · no gnomAD frequency available for this variant

## For patients & families {#patients}

This is a change in the BPTF gene that is considered likely disease-causing, submitted by 1 submitter, and is linked to neurodevelopmental disorder with dysmorphic facies and distal limb anomalies.

*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/0018513/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [BPTF](https://sugi.bio/atlas/gene/BPTF/) |
| Protein change (HGVS p.) | p.Pro1855fs |
| Coding change (HGVS c.) | c.5564del |
| MANE Select transcript | [NM_182641](https://www.ncbi.nlm.nih.gov/nuccore/NM_182641) |
| dbSNP | [rs2147246788](https://www.ncbi.nlm.nih.gov/snp/rs2147246788/) |
| Variant type | Deletion |
| Location | chr17:67922845-67922845 (GRCh38) |
| ClinVar | [VCV1341680](https://www.ncbi.nlm.nih.gov/clinvar/variation/1341680/) |

**All HGVS expressions:** `NC_000017.10:g.65918962del`, `NC_000017.11:g.67922846del`, `NG_052828.1:g.102330del`, `NM_004459.7:c.5942del`, `NM_182641.4:c.5564del`

## 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 0.479, GERP -1.48, phastCons 0.799 — weakly conserved position
- Molecular consequence: **frameshift** — a predicted loss-of-function variant. ClinGen curates **sufficient evidence for haploinsufficiency** in this gene (constraint LOEUF 0.09, 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 14 of 28**, 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.
- Repeat context: **segmental_duplication** (chr17:32113096). 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}

**BPTF** population constraint: LOEUF 0.09, pLI 1, missense-Z 5.0945; ClinGen dosage — haploinsufficiency 3/3, triplosensitivity 0/3. *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):

- **syndromic intellectual disability** — Definitive (AD)

## Protein context {#protein}


**46 experimental structure(s)** (PDB): [2F6J](https://www.rcsb.org/structure/2F6J), [2F6N](https://www.rcsb.org/structure/2F6N), [2FSA](https://www.rcsb.org/structure/2FSA), [2FUI](https://www.rcsb.org/structure/2FUI), [2FUU](https://www.rcsb.org/structure/2FUU), [2RI7](https://www.rcsb.org/structure/2RI7) — incl. mutant structure 2RI7.

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

*Describes the biological roles of BPTF (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:** BPTF's established molecular role includes sequence-specific DNA binding.


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

**Molecular function:** sequence-specific DNA binding.

**Biological process:** negative regulation of transcription by RNA polymerase II, chromatin remodeling, regulation of DNA-templated transcription, regulation of transcription by RNA polymerase II, brain development, positive regulation of transcription by RNA polymerase II.

## Clinical significance {#significance}

**Likely pathogenic** — review status No assertion criteria *(no assertion criteria provided)*, last evaluated 2021-05-27.

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

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Department of Endocrinology and Genetics, Fuzhou Children’s Hospital of Fujian Medical University | Likely pathogenic | no assertion criteria provided | provider interpretation | 2021-05-27 |

## Associated conditions {#conditions}

[neurodevelopmental disorder with dysmorphic facies and distal limb anomalies](https://sugi.bio/atlas/disease/neurodevelopmental-disorder-with-dysmorphic-facies-and-distal-limb-anomalies/).

**Reported phenotype names (ClinVar):** Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies.

## Similar variants {#similar}

Related BPTF variant pages (same residue, condition, or type): [BPTF p.Arg2854fs](/variant/bptf-p-arg2854fs), [BPTF p.Asp2751fs](/variant/bptf-p-asp2751fs), [BPTF p.Gly94fs](/variant/bptf-p-gly94fs), [BPTF p.His1985fs](/variant/bptf-p-his1985fs), [BPTF p.Leu330fs](/variant/bptf-p-leu330fs), [BPTF p.Lys1053fs](/variant/bptf-p-lys1053fs), [BPTF p.Thr1819fs](/variant/bptf-p-thr1819fs), [BPTF p.Val2188fs](/variant/bptf-p-val2188fs).

### 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 1341680). 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.*