# NM_004357.5(CD151):c.219G>A (p.Val73=)

https://sugi.bio/variant/cd151-p-val73

## Summary

**CD151 p.Val73= (c.219G>A)** is classified **Uncertain significance** in CD151 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-30). Very rare (popmax 0.00133%, afr); Associated with epidermolysis bullosa simplex 7, with nephropathy and deafness.

**At a glance:** Uncertain significance · review: Single submitter · 1 submitter · 1 linked condition · very rare (popmax 0.00133%, afr)

## For patients & families {#patients}

This is a change in the CD151 gene that is currently of uncertain significance — a definitive interpretation has not yet been established, 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.Val73= |
| Coding change (HGVS c.) | c.219G>A |
| MANE Select transcript | [NM_004357](https://www.ncbi.nlm.nih.gov/nuccore/NM_004357) |
| Variant type | single nucleotide variant |
| Location | chr11:836385-836385 (GRCh38) |
| ClinVar | [VCV3574086](https://www.ncbi.nlm.nih.gov/clinvar/variation/3574086/) |

**All HGVS expressions:** `LRG_817:g.8434G>A`, `LRG_817t1:c.219G>A`, `NC_000011.10:g.836385G>A`, `NC_000011.9:g.836385G>A`, `NG_007478.1:g.8434G>A`, `NM_001039490.2:c.219G>A`, `NM_004357.5:c.219G>A`, `NM_139029.2:c.219G>A`, `NM_139030.4:c.219G>A`

## 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 and, for splice-region changes, SpliceAI (below), not from a missing predictor score.
- SpliceAI predicts **donor gain** (Δ 0.63) — a splice-altering prediction on an uncertain variant — a signal for review
- Conservation: phyloP 3.194, GERP -4.06, phastCons 1 — highly conserved position (PP3-type support)
- CADD: **PHRED 17.93**. No single ClinGen-calibrated threshold exists and the expert panels that use CADD disagree — GUCY2D/AIPL1 require ≥ 20.0 for an untranslated-region variant, ABCA4 ≥ 28.1 for a synonymous or indel variant, the Pulmonary Hypertension panel imports Pejaver 2022's missense-calibrated numbers, and the Antibody Deficiencies panel declines CADD entirely for PIK3CD. CADD v1.7 also incorporates Zoonomia phyloP, so it partly re-expresses the conservation above. *Descriptive; no threshold applied.*
- SpliceAI deltas (raw): acceptor loss **0.00**, donor loss **0.00**, acceptor gain **0.00**, donor gain **0.63**. Largest is donor gain.
- SpliceAI deltas (masked): acceptor loss **0.00**, donor loss **0.00**, acceptor gain **0.00**, donor gain **0.63**.
- Pangolin: Δ**0.25** (gain), gain 0.25 / loss 0.00. Agrees with SpliceAI. An independent predictor to SpliceAI — a different model trained on different data. *Descriptive; ClinGen's SVI calibration covers SpliceAI, not Pangolin, so no ACMG code is assigned.*
- Population frequency (gnomAD v4.1): grpmax **0.00133%** (afr) · 1/74,940 in the highest group · 2/1,612,306 alleles overall — very rare (popmax 0.00133%, afr).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| African / African-American (grpmax) | 0.00133% | 74,940 |
| European (non-Finnish) | 8.48e-05% | 1,179,928 |

*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}

**Uncertain significance** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2024-03-30.

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

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Fulgent Genetics, Fulgent Genetics | Uncertain significance | criteria provided, single submitter | clinical testing | 2024-03-30 |

## 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.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), [CD151 p.Ala81Thr](/variant/cd151-p-ala81thr), [CD151 p.Arg133Cys](/variant/cd151-p-arg133cys), [CD151 p.Arg165Gln](/variant/cd151-p-arg165gln).

### 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 3574086). 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.*