# NM_022336.3(EDAR):c.(?_998)_(1347_?)del

https://sugi.bio/variant/edar-c-998

## Summary

**EDAR c.(?_998** is classified **Pathogenic** in EDAR (ClinVar, Single submitter, 1 submitter; last evaluated 2014-01-22). Associated with autosomal dominant hypohidrotic ectodermal dysplasia.

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

> **Built without this gene's context.** ClinVar files this variant under an overlapping gene, so its own gene's record set does not contain it and this page is assembled from the variant alone. Gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up — absent from this page, not from the data.

## For patients & families {#patients}

This is a change in the EDAR gene that is reported as disease-causing, but on limited review, submitted by 1 submitter, and is linked to autosomal dominant hypohidrotic ectodermal dysplasia.

*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, X-linked recessive |
| Age of onset (of this condition) | Infancy, Neonatal |
| Prevalence | 1-9 / 100 000 (Europe) |

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

- Abnormality of the dentition — Very frequent (99-80%)
- Hypoplasia of the maxilla — Very frequent (99-80%)
- Dry skin — Very frequent (99-80%)
- Thin skin — Very frequent (99-80%)
- Keratoconjunctivitis sicca — Very frequent (99-80%)
- Abnormal facial shape — Very frequent (99-80%)
- Abnormal dental morphology — Very frequent (99-80%)
- Irregular hyperpigmentation — Very frequent (99-80%)

**Support & next steps:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0002048/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [EDAR](https://sugi.bio/atlas/gene/EDAR/) |
| Coding change (HGVS c.) | c.(?_998 |
| MANE Select transcript | [NM_022336](https://www.ncbi.nlm.nih.gov/nuccore/NM_022336) |
| Variant type | Deletion |
| Location | chr2:None-None (GRCh38) |
| ClinVar | [VCV163325](https://www.ncbi.nlm.nih.gov/clinvar/variation/163325/) |

**All HGVS expressions:** `NC_000002.11:g.(?_109513363)_(109522790_?)del`, `NC_000002.12:g.(?_108896907)_(108906334_?)del`, `NM_022336.3:c.(?_998)_(1347_?)del`

## Clinical significance {#significance}

**Pathogenic** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2014-01-22.

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

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Pathogenic | criteria provided, single submitter | clinical testing | 2014-01-22 |

## Associated conditions {#conditions}

[autosomal dominant hypohidrotic ectodermal dysplasia](https://sugi.bio/atlas/disease/autosomal-dominant-hypohidrotic-ectodermal-dysplasia/).

**Reported phenotype names (ClinVar):** Autosomal dominant hypohidrotic ectodermal dysplasia, Autosomal dominant hypohidrotic ectodermal dysplasia syndrome.

### 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 163325). 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.*