# NM_001142800.2(EYS):c.2420del (p.Ser807fs)

https://sugi.bio/variant/eys-p-ser807fs

## Summary

**EYS p.Ser807fs (c.2420del)** is classified **Pathogenic** in EYS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-01). No gnomAD frequency available for this variant; Associated with retinitis pigmentosa.

**At a glance:** Pathogenic · review: Multiple submitters · rsID rs1768038999 · 2 submitters · 1 linked condition · no gnomAD frequency available for this variant

## For patients & families {#patients}

This is a change in the EYS gene that is considered disease-causing, submitted by 2 submitters, and is linked to retinitis pigmentosa.

*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 dominant, Autosomal recessive, Mitochondrial inheritance |
| Age of onset (of this condition) | Adolescent, Adult, Childhood |
| Prevalence | 1-5 / 10 000 (Europe) |
| Clinical trials | 238 registered for this condition — see ClinicalTrials.gov |
| Diagnostic panels | EYS is a diagnostic-grade gene on 1 Genomics England panel |

**Commonly reported features of Retinitis pigmentosa** (across patients with this condition; presentation varies — frequencies from Orphanet):

- Conductive hearing impairment — Very frequent (99-80%)
- Sensorineural hearing impairment — Very frequent (99-80%)
- Visual impairment — Very frequent (99-80%)
- Abnormal electroretinogram — Very frequent (99-80%)
- Retinal degeneration — Very frequent (99-80%)
- Photophobia — Very frequent (99-80%)
- Blindness — Very frequent (99-80%)
- Nystagmus — Very frequent (99-80%)

**Support & next steps:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0005694/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [EYS](https://sugi.bio/atlas/gene/EYS/) |
| Protein change (HGVS p.) | p.Ser807fs |
| Coding change (HGVS c.) | c.2420del |
| MANE Select transcript | [NM_001142800](https://www.ncbi.nlm.nih.gov/nuccore/NM_001142800) |
| dbSNP | [rs1768038999](https://www.ncbi.nlm.nih.gov/snp/rs1768038999/) |
| Variant type | Deletion |
| Location | chr6:64912705-64912705 (GRCh38) |
| ClinVar | [VCV813175](https://www.ncbi.nlm.nih.gov/clinvar/variation/813175/) |

**All HGVS expressions:** `NC_000006.11:g.65622598del`, `NC_000006.12:g.64912705del`, `NG_023443.2:g.799521del`, `NM_001142800.2:c.2420del`, `NM_001292009.2:c.2420del`

## 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 2.45, phastCons 0.885 — highly conserved position (PP3-type support)
- Molecular consequence: **frameshift** — a predicted loss-of-function variant. Gene population constraint: LOEUF 0.96, pLI 6.4354e-50. *Descriptive; not an applied PVS1 code.*
- Nonsense-mediated decay: the premature termination codon is **in exon 16 of 43**, 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}

**EYS** population constraint: LOEUF 0.96, pLI 6.4354e-50, missense-Z -0.45186. *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):

- **EYS-related retinopathy** — Definitive (AR)

## Protein context {#protein}

Residue **807** lies in the egf-like 10; calcium-binding domain.

## Clinical significance {#significance}

**Pathogenic** — review status Multiple submitters *(criteria provided, multiple submitters, no conflicts)*, last evaluated 2025-04-01.

**Submitter consensus:** unanimous (2/2 Pathogenic).

**Submission history:** 2 submissions (2020–2025); classifications have been stable.

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Molecular Genetics Laboratory, Institute for Ophthalmic Research | Pathogenic | criteria provided, single submitter | research | 2020-01-09 |
| CeGaT Center for Human Genetics Tuebingen | Pathogenic | criteria provided, single submitter | clinical testing | 2025-04-01 |

## Associated conditions {#conditions}

[retinitis pigmentosa](https://sugi.bio/atlas/disease/retinitis-pigmentosa/).

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

## Similar variants {#similar}

Related EYS variant pages (same residue, condition, or type): [EYS c.5928-3_5928-1del](/variant/eys-c-5928-minus-3-5928-minus-1del), [EYS p.Asn2855fs](/variant/eys-p-asn2855fs), [EYS p.Cys2350fs](/variant/eys-p-cys2350fs), [EYS p.Cys78fs](/variant/eys-p-cys78fs), [EYS p.Gln2267fs](/variant/eys-p-gln2267fs), [EYS p.Gln2723fs](/variant/eys-p-gln2723fs), [EYS p.Glu176del](/variant/eys-p-glu176del), [EYS p.Ile1451fs](/variant/eys-p-ile1451fs).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-14); 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 813175). 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.*