# NM_000501.4(ELN):c.1748del (p.Val583fs)

https://sugi.bio/variant/eln-p-val583fs

## Summary

**ELN p.Val583fs (c.1748del)** is classified **Pathogenic** in ELN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-08). No gnomAD frequency available for this variant; Associated with supravalvular aortic stenosis.

**At a glance:** Pathogenic · review: Single submitter · rsID rs2486383085 · 1 submitter · 1 linked condition · no gnomAD frequency available for this variant

## For patients & families {#patients}

This is a change in the ELN gene that is reported as disease-causing, but on limited review, submitted by 1 submitter, and is linked to supravalvular aortic stenosis.

*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.*

|  |  |
| --- | --- |
| Clinical trials | 3 registered for this condition — see ClinicalTrials.gov |

**Support & next steps:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0000743/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [ELN](https://sugi.bio/atlas/gene/ELN/) |
| Protein change (HGVS p.) | p.Val583fs |
| Coding change (HGVS c.) | c.1748del |
| dbSNP | [rs2486383085](https://www.ncbi.nlm.nih.gov/snp/rs2486383085/) |
| Variant type | Deletion |
| Location | chr7:74061101-74061101 (GRCh38) |
| ClinVar | [VCV2628092](https://www.ncbi.nlm.nih.gov/clinvar/variation/2628092/) |

**All HGVS expressions:** `NC_000007.13:g.73475431del`, `NC_000007.14:g.74061101del`, `NG_009261.1:g.38005del`, `NM_000501.4:c.1748del`, `NM_001081752.3:c.1661del`, `NM_001081753.3:c.1706del`, `NM_001081754.3:c.1763del`, `NM_001081755.3:c.1691del`, `NM_001278912.2:c.1748del`, `NM_001278913.2:c.1505del`, `NM_001278914.2:c.1676del`, `NM_001278915.2:c.1766del`, `NM_001278916.2:c.1604del`, `NM_001278917.2:c.1718del`, `NM_001278918.2:c.1481del`, `NM_001278939.2:c.1934del`

## 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 11.016, GERP 6.38, phastCons 1 — highly conserved position (PP3-type support)
- Molecular consequence: **frameshift** — a predicted loss-of-function variant. For a truncating variant the loss-of-function impact is position-dependent — C-terminal / last-exon truncations may escape nonsense-mediated decay. *Descriptive; not an applied PVS1 code.*
- SpliceAI: **not looked up on this page** — it was served without the gene's SpliceAI index, so no lookup was made. This is a gap in this page, not in the data, and says nothing about whether a splicing effect is predicted.
- 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.*

## Clinical significance {#significance}

**Pathogenic** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2023-09-08.

**Submitter consensus:** unanimous (1/1 Pathogenic).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| KardioGenetik, Herz- und Diabeteszentrum NRW | Pathogenic | criteria provided, single submitter | clinical testing | 2023-09-08 |

## Associated conditions {#conditions}

[supravalvular aortic stenosis](https://sugi.bio/atlas/disease/supravalvular-aortic-stenosis/).

**Reported phenotype names (ClinVar):** Supravalvar aortic stenosis, Supravalvar aortic stenosis, Eisenberg type.

### 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 2628092). 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.*