# NM_004357.5(CD151):c.203dup (p.Thr69fs)

https://sugi.bio/variant/cd151-p-thr69fs

## Summary

**CD151 p.Thr69fs (c.203dup)** is classified **Likely pathogenic** in CD151 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-21). Associated with epidermolysis bullosa simplex 7, with nephropathy and deafness.

**At a glance:** Likely pathogenic · review: Single submitter · 1 submitter · 1 linked condition

## For patients & families {#patients}

This is a change in the CD151 gene that is considered likely disease-causing, submitted by 1 submitter, and is linked to epidermolysis bullosa simplex 7, with nephropathy and deafness.

*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.*

|  |  |
| --- | --- |
| Typical inheritance (of this condition) | Autosomal recessive |
| Age of onset (of this condition) | Adolescent |
| Diagnostic panels | CD151 is a diagnostic-grade gene on 4 Genomics England panels |

**Support & next steps:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0017367/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [CD151](https://sugi.bio/atlas/gene/CD151/) |
| Protein change (HGVS p.) | p.Thr69fs |
| Coding change (HGVS c.) | c.203dup |
| MANE Select transcript | [NM_004357](https://www.ncbi.nlm.nih.gov/nuccore/NM_004357) |
| Variant type | Duplication |
| Location | chr11:836366-836367 (GRCh38) |
| ClinVar | [VCV3574085](https://www.ncbi.nlm.nih.gov/clinvar/variation/3574085/) |

**All HGVS expressions:** `LRG_817:g.8418dup`, `LRG_817t1:c.203dup`, `NC_000011.10:g.836369dup`, `NC_000011.9:g.836369dup`, `NG_007478.1:g.8418dup`, `NM_001039490.2:c.203dup`, `NM_004357.5:c.203dup`, `NM_139029.2:c.203dup`, `NM_139030.4:c.203dup`

## 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 7.471, GERP 2.03, phastCons 1 — highly conserved position (PP3-type support)
- Molecular consequence: **frameshift** — a predicted loss-of-function variant. Gene population constraint: LOEUF 0.816, pLI 0.00056955. *Descriptive; not an applied PVS1 code.*
- Nonsense-mediated decay: the premature termination codon is **in exon 4 of 9**, so the transcript is predicted to undergo NMD.
- SpliceAI: **not assessed** — the release is built from a substitutions-only source, so it holds no duplication variants. That is a property of the dataset, not of the variant, and is not evidence against a splicing effect.

*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}

**CD151** population constraint: LOEUF 0.816, pLI 0.00056955, missense-Z 0.62523. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 88.02, 68% of residues very-high.

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

*Describes the biological roles of CD151 (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:** CD151's established molecular role includes integrin binding.


### Pathways affected {#pathways}

CD151 participates in **2 Reactome pathways** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [Assembly of collagen fibrils and other multimeric structures](https://reactome.org/content/detail/R-HSA-2022090) | curated |
| [Type I hemidesmosome assembly](https://reactome.org/content/detail/R-HSA-446107) | curated |

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

**Molecular function:** integrin binding.

**Biological process:** positive regulation of cell migration, wound healing, spreading of cells, positive regulation of endocytosis.

## Clinical significance {#significance}

**Likely pathogenic** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2024-03-21.

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

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Fulgent Genetics, Fulgent Genetics | Likely pathogenic | criteria provided, single submitter | clinical testing | 2024-03-21 |

## Associated conditions {#conditions}

[epidermolysis bullosa simplex 7, with nephropathy and deafness](https://sugi.bio/atlas/disease/epidermolysis-bullosa-simplex-7-with-nephropathy-and-deafness/).

**Reported phenotype names (ClinVar):** Epidermolysis bullosa simplex 7, with nephropathy and deafness, RAPH BLOOD GROUP SYSTEM, Nephrotic syndrome - deafness - pretibial epidermolysis bullosa syndrome, Nephropathy with Pretibial Epidermolysis Bullosa and Deafness, MER2 BLOOD CELL ANTIGEN EXPRESSION.

## Similar variants {#similar}

Related CD151 variant pages (same residue, condition, or type): [CD151 p.Tyr48fs](/variant/cd151-p-tyr48fs), [CD151 p.Thr69=](/variant/cd151-p-thr69), [CD151 p.Asp128fs](/variant/cd151-p-asp128fs), [CD151 p.Lys7Ter](/variant/cd151-p-lys7ter), [CD151 c.352-11C>G](/variant/cd151-c-352-minus-11c-g), [CD151 c.702+4A>G](/variant/cd151-c-702-plus-4a-g), [CD151 c.702+5G>C](/variant/cd151-c-702-plus-5g-c), [CD151 p.Ala145Thr](/variant/cd151-p-ala145thr).

### 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 3574085). 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.*