ASCL3 p.Ala138Glu
c.413C>A · VCV3952081
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.942 | strongly pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 2.1, phastCons 1 |
| Regional constraint | o/e 1.06 | unconstrained · MANE · 542 bp · p 0.35 · regional, not allelic |
| Overall | ||
| CADD | 29.9 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,880 alleles
Overall
0.000137%
2/1,461,866 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,880 |
| African / African-American | 0.00133% | 75,014 |
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
- ASCL3
- Protein
- p.Ala138Glu
- Coding
- c.413C>A
- MANE Select
- NM_020646
- Type
- single nucleotide variant
- Location
- chr11:8937749 (GRCh38)
- Gene constraint
- LOEUF 1.504 · pLI 0.06 (gnomAD)
- Structure
- AlphaFold pLDDT 69.74
- Residue 138
- the bhlh domain; the 'helix-loop-helix motif' region
Similar variants
- ASCL3 p.Ala114Thr Uncertain significance ★ same type
- ASCL3 p.Ala154Thr Uncertain significance ★ same type
- ASCL3 p.Ala93Gly Uncertain significance ★ same type
- ASCL3 p.Arg101Trp Uncertain significance ★ same type
- ASCL3 p.Arg105Gln Uncertain significance ★ same type
- ASCL3 p.Arg117Cys Uncertain significance ★ same type
- ASCL3 p.Arg22Cys Uncertain significance ★ same type
- ASCL3 p.Arg55Trp Uncertain significance ★ 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/ascl3-p-ala138glu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown