Is AMELX p.Pro144fs (c.431del) pathogenic?

AMELX p.Pro144fs (c.431del) is classified Likely pathogenic in AMELX (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-03-20). Very rare (popmax 0.000112%, nfe); Associated with amelogenesis imperfecta type 1E.

What condition is associated with AMELX p.Pro144fs (c.431del)?

AMELX p.Pro144fs (c.431del) is associated with amelogenesis imperfecta type 1E (ClinVar).

How common is AMELX p.Pro144fs (c.431del) in the general population?

AMELX p.Pro144fs (c.431del) is very rare (popmax 0.000112%, nfe) (gnomAD).

AMELX p.Pro144fs

c.431del · rs387906489 · VCV11139

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Conditions

amelogenesis imperfecta type 1E

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.9	GERP 0.87, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000112% European (non-Finnish) · 1/895,151 alleles

Overall 9.11e-05% 1/1,097,923 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: AMELX
Protein: p.Pro144fs
Coding: c.431del
MANE Select: NM_013427 · reported on NM_001142
dbSNP: rs387906489
Type: Deletion
Location: chrX:11298833 (GRCh38)

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

Disease context

amelogenesis imperfecta type 1E — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-pro144fs (accessed [today's date]).

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