ASCC3 p.Pro746=
c.2238C>T · VCV4893572
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.393%, 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 1.5 | GERP 0.92, phastCons 1 |
| Overall | ||
| CADD | 3.847 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.393%
African / African-American · 295/74,996 alleles
Filtering AF
0.356%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.342%
Overall
0.0226%
364/1,613,624 alleles · rare
exomes 176/1,461,400 · genomes 188/152,224 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.393% | 254 |
| Admixed American | 0.0467% | 2,143 |
| Remaining individualsnot grpmax-eligible | 0.04% | 2,499 |
| European (non-Finnish) | 0.00136% | 73,735 |
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
- ASCC3
- Protein
- p.Pro746=
- Coding
- c.2238C>T
- MANE Select
- NM_006828
- Type
- single nucleotide variant
- Location
- chr6:100679666 (GRCh38)
- Gene constraint
- LOEUF 0.677 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.93 · 2 PDB
- Residue 746
- the helicase c-terminal 1 domain; an α-helix
Similar variants
- ASCC3 c.1597-2A>G Likely pathogenic ★★ same type
- ASCC3 c.1596+1G>T Uncertain significance ★★ same type
- ASCC3 p.Ala1186Val Uncertain significance ★★ ⚠ same type
- ASCC3 p.Ala94Val Uncertain significance ★★ ⚠ same type
- ASCC3 p.Arg1808His Uncertain significance ★★ ⚠ same type
- ASCC3 p.Arg1835Cys Uncertain significance ★★ ⚠ same type
- ASCC3 p.Arg630Cys Uncertain significance ★★ ⚠ same type
- ASCC3 p.Asn1607Ser 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/ascc3-p-pro746 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown