ASCL4 p.Pro100Thr
c.298C>A · rs781541284 · VCV2351101
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.026%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.858 | moderately pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7 | GERP 1.6, phastCons 1 |
| Regional constraint | o/e 1.28 | unconstrained · MANE · 515 bp · p 5.2e-06 · regional, not allelic |
| Overall | ||
| CADD | 28.9 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.026%
European (non-Finnish) · 304/1,167,648 alleles
Filtering AF
0.0236%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0227%
Overall
0.0209%
329/1,572,344 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.026% | 3,841 |
| Remaining individualsnot grpmax-eligible | 0.0212% | 4,722 |
| Admixed American | 0.0181% | 5,530 |
| African / African-American | 0.00269% | 37,197 |
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
- ASCL4
- Protein
- p.Pro100Thr
- Coding
- c.298C>A
- MANE Select
- NM_203436
- dbSNP
- rs781541284
- Type
- single nucleotide variant
- Location
- chr12:107775516 (GRCh38)
- Gene constraint
- LOEUF 1.921 · pLI 0.13 (gnomAD)
- Structure
- AlphaFold pLDDT 71.48
- Residue 100
- the bhlh domain
Similar variants
- ASCL4 p.Ala141Thr Uncertain significance ★ same type
- ASCL4 p.Ala157Ser Uncertain significance ★ same type
- ASCL4 p.Ala160Val Uncertain significance ★ same type
- ASCL4 p.Ala50Glu Uncertain significance ★ same type
- ASCL4 p.Ala68Thr Uncertain significance ★ same type
- ASCL4 p.Arg115Cys Uncertain significance ★ same type
- ASCL4 p.Arg32Gln Uncertain significance ★ same type
- ASCL4 p.Arg33Gly 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/ascl4-p-pro100thr (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown