ALX3 p.Pro28=
c.84G>A · rs1011770350 · VCV742297
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00318%, eas)
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 0.67 | GERP -2.2, phastCons 1 |
| Overall | ||
| CADD | 10.13 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00318%
East Asian · 1/31,436 alleles
Filtering AF
0.000517%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000193%
Overall
0.000311%
4/1,287,098 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00318% | 31,436 |
| African / African-American | 0.00311% | 32,119 |
| European (non-Finnish) | 9.83e-05% | 1,017,450 |
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
- ALX3
- Protein
- p.Pro28=
- Coding
- c.84G>A
- MANE Select
- NM_006492
- dbSNP
- rs1011770350
- Type
- single nucleotide variant
- Location
- chr1:110070529 (GRCh38)
- Gene constraint
- LOEUF 1.051 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.90
- Residue 28
- the 'disordered' region
Similar variants
- ALX3 p.Pro250Leu Uncertain significance ★★ ⚠ same type
- ALX3 p.Pro40Ala Uncertain significance ★★ ⚠ same type
- ALX3 p.Ser131Arg Uncertain significance ★★ ⚠ same type
- ALX3 p.Tyr320Cys Uncertain significance ★★ ⚠ same type
- ALX3 c.277+33C>T Benign ★★ same type
- ALX3 p.Arg209= Benign/Likely benign ★★ same type
- ALX3 p.Pro138= Benign/Likely benign ★★ same type
- ALX3 p.Pro250Ala Benign/Likely 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/alx3-p-pro28 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown