Is AMELX p.Pro48fs (c.143del) pathogenic?

AMELX p.Pro48fs (c.143del) is classified Pathogenic in AMELX (ClinVar, No assertion criteria, 1 submitter; last evaluated 2018-07-24). Absent from gnomAD; Associated with amelogenesis imperfecta.

What condition is associated with AMELX p.Pro48fs (c.143del)?

AMELX p.Pro48fs (c.143del) is associated with amelogenesis imperfecta (ClinVar).

How common is AMELX p.Pro48fs (c.143del) in the general population?

AMELX p.Pro48fs (c.143del) is absent from gnomAD (gnomAD).

How is Amelogenesis imperfecta inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

AMELX p.Pro48fs

c.143del · rs1603038146 · VCV617639

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

amelogenesis imperfecta

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.3	GERP -1.9, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: AMELX
Protein: p.Pro48fs
Coding: c.143del
MANE Select: NM_001142
dbSNP: rs1603038146
Type: Deletion
Location: chrX:11298275 (GRCh38)
Structure: AlphaFold pLDDT 59.51

Full AMELX gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

amelogenesis imperfecta — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Amelogenesis imperfecta (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked dominant
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (United States)

Similar variants

AMELX p.Pro48Leu Uncertain significance ★ ⚠ same residue
AMELX c.103-116T>C Pathogenic same condition
AMELX p.Asn30His Pathogenic ⚠ same condition
AMELX p.Ile5_Ala8delinsThr Pathogenic same type
AMELX p.Tyr127fs Pathogenic same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/amelx-p-pro48fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown