# NM_001142.2(AMELX):c.113del (p.Pro38fs)

https://sugi.bio/variant/amelx-p-pro38fs

## Summary

**AMELX p.Pro38fs (c.113del)** is classified **Pathogenic** in AMELX (ClinVar, No assertion criteria, 1 submitter; last evaluated 2002-04-01). Very rare (popmax 0.00156%, nfe); Associated with amelogenesis imperfecta type 1E.

**At a glance:** Pathogenic · review: No assertion criteria · rsID rs387906487 · 1 submitter · 1 linked condition · very rare (popmax 0.00156%, nfe)

## For patients & families {#patients}

This is a change in the AMELX gene that is reported as disease-causing, but on limited review, submitted by 1 submitter, and is linked to amelogenesis imperfecta type 1E.

*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.*

**Support & next steps:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0009943/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [AMELX](https://sugi.bio/atlas/gene/AMELX/) |
| Protein change (HGVS p.) | p.Pro38fs |
| Coding change (HGVS c.) | c.113del |
| MANE Select transcript | [NM_013427](https://www.ncbi.nlm.nih.gov/nuccore/NM_013427) (variant reported on NM_001142) |
| dbSNP | [rs387906487](https://www.ncbi.nlm.nih.gov/snp/rs387906487/) |
| Variant type | Deletion |
| Location | chrX:11298243-11298243 (GRCh38) |
| ClinVar | [VCV11137](https://www.ncbi.nlm.nih.gov/clinvar/variation/11137/) |

**All HGVS expressions:** `NC_000023.10:g.11316366del`, `NC_000023.11:g.11298246del`, `NG_012040.1:g.9834del`, `NG_012040.2:g.9835del`, `NG_012494.2:g.372459del`, `NM_001142.2:c.113del`, `NM_001287242.2:c.49-43536del`, `NM_006125.3:c.589-43536del`, `NM_013427.3:c.589-43536del`, `NM_182680.1:c.155del`, `NM_182681.1:c.65del`

## 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 10.856, GERP 1.71, 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 (gnomAD v4.1): grpmax **0.00156%** (nfe) · FAF95 0.000907% · FAF99 0.00071% · 14/895,183 in the highest group · 14/1,097,814 alleles overall — very rare (popmax 0.00156%, nfe).

*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 No assertion criteria *(no assertion criteria provided)*, last evaluated 2002-04-01.

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

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| OMIM | Pathogenic | no assertion criteria provided | literature only | 2002-04-01 |

## Associated conditions {#conditions}

[amelogenesis imperfecta type 1E](https://sugi.bio/atlas/disease/amelogenesis-imperfecta-type-1e/).

**Reported phenotype names (ClinVar):** Amelogenesis imperfecta type 1E, Amelogenesis imperfecta, hypomaturation type, with snow-capped teeth, Amelogenesis imperfecta X-linked 1, Enamel hypoplasia X-linked, ENAMEL HYPOPLASIA, X-LINKED 1, Amelogenesis Imperfecta, Hypoplastic/Hypomaturation, X-Linked 1.

### 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 11137). 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.*