AMELX p.Pro75=
c.225G>A · rs142884100 · VCV3051823
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.119%, eas)
Conditions
1
AMELX-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.20 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 4.6 | GERP -0.37, phastCons 1 |
| Overall | ||
| CADD | 11.71 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.119%
East Asian · 40/33,696 alleles
Filtering AF
0.0896%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0794%
Overall
0.00414%
50/1,207,864 alleles · rare
exomes 46/1,098,213 · genomes 4/109,651 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.119% | 842 |
| African / African-American | 0.00355% | 28,203 |
| Remaining individualsnot grpmax-eligible | 0.0021% | 47,576 |
| European (non-Finnish) | 0.000782% | 127,819 |
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.Pro75=
- Coding
- c.225G>A
- MANE Select
- NM_001142
- dbSNP
- rs142884100
- Type
- single nucleotide variant
- Location
- chrX:11298628 (GRCh38)
- Structure
- AlphaFold pLDDT 59.51
Disease context
AMELX-related disorder
Similar variants
- AMELX p.Pro75Leu Uncertain significance ★ ⚠ same residue
- AMELX p.Met1Ile Likely pathogenic ★★ same condition
- AMELX p.Pro56Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
- AMELX c.103-1G>A Likely pathogenic ★ same condition
- AMELX p.Gln141Ter Likely pathogenic ★ same condition
- AMELX p.Pro122= Likely benign same condition
- AMELX c.103-111A>G Uncertain significance ★★ same type
- AMELX c.54+65T>C Benign ★★ 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-pro75 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown