ASXL3 p.Pro718=
c.2154G>A · rs370185733 · VCV444429
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00401%, afr)
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 -1.7 | GERP -5.2 |
| Overall | ||
| CADD | 1.01 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00401%
African / African-American · 3/74,892 alleles
Filtering AF
0.00106%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000787%
Overall
0.00155%
25/1,613,750 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00401% | 24,964 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,608 |
| South Asian | 0.00329% | 30,362 |
| European (non-Finnish) | 0.00153% | 65,548 |
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
- ASXL3
- Protein
- p.Pro718=
- Coding
- c.2154G>A
- MANE Select
- NM_030632
- dbSNP
- rs370185733
- Type
- single nucleotide variant
- Location
- chr18:33739558 (GRCh38)
- Gene constraint
- LOEUF 0.229 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 39.70
- Residue 718
- the 'disordered' region
Similar variants
- ASXL3 p.Pro718Leu Uncertain significance ★ ⚠ same residue
- ASXL3 p.Pro718Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
- ASXL3 c.3039+1G>A Pathogenic ★★ same type
- ASXL3 p.Arg1036Ter Pathogenic/Likely pathogenic ★★ same type
- ASXL3 p.Arg1068Ter Pathogenic/Likely pathogenic ★★ same type
- ASXL3 p.Arg1117Ter Pathogenic/Likely pathogenic ★★ same type
- ASXL3 p.Arg1444Ter Pathogenic/Likely pathogenic ★★ same type
- ASXL3 p.Arg1467Ter 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/asxl3-p-pro718 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown