Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 28.7%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.88 | GERP -3.4 |
| Overall | ||
| CADD | 4.448 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
28.7%
African / African-American · 16,110/56,157 alleles
Filtering AF
28.3%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 28.2%
Overall
20.3%
245,578/1,207,173 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 28.7% | 3 |
| Finnishnot grpmax-eligible | 28.5% | 4 |
| Middle Eastern | 26.7% | 4 |
| Ashkenazi Jewishnot grpmax-eligible | 24.2% | 4 |
| European (non-Finnish) | 20.6% | 5 |
| Remaining individualsnot grpmax-eligible | 19.9% | 5 |
| South Asian | 17.4% | 6 |
| Admixed American | 10.9% | 9 |
| East Asian | 3.26% | 31 |
| Amishnot grpmax-eligible | 2.52% | 40 |
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.His73=
- Coding
- c.219C>T
- MANE Select
- NM_001142
- dbSNP
- rs2106416
- Type
- single nucleotide variant
- Location
- chrX:11298622 (GRCh38)
- Structure
- AlphaFold pLDDT 59.51
Similar variants
- AMELX p.Met1Ile Likely pathogenic ★★ same type
- AMELX p.Pro56Thr Pathogenic/Likely pathogenic ★★ ⚠ same type
- AMELX c.103-111A>G Uncertain significance ★★ same type
- AMELX c.54+65T>C Benign ★★ same type
- AMELX c.103-1G>A Likely pathogenic ★ same type
- AMELX c.144+1G>A Likely pathogenic ★ same type
- AMELX p.Gln141Ter Likely pathogenic ★ same type
- AMELX p.Trp4Ter Likely 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-his73 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown