MCM4 p.Ser228=
c.684T>C · VCV4749227
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0169%, mid)
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 1.1 | GERP -0.69, phastCons 1 |
| Overall | ||
| CADD | 8.51 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0169%
Middle Eastern · 1/5,920 alleles
Overall
0.000189%
3/1,583,476 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0169% | 5,920 |
| East Asian | 0.00224% | 44,674 |
| African / African-American | 0.00136% | 73,690 |
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
- MCM4
- Protein
- p.Ser228=
- Coding
- c.684T>C
- MANE Select
- NM_182746
- Type
- single nucleotide variant
- Location
- chr8:47963031 (GRCh38)
- Gene constraint
- LOEUF 0.806 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.25 · 28 PDB
- Residue 228
- an α-helix
Similar variants
- MCM4 p.Ser228Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
- MCM4 p.Ser228Phe Uncertain significance ★ ⚠ same residue
- MCM4 c.71-2A>G Pathogenic ★★ same type
- MCM4 c.-74C>T Uncertain significance ★★ same type
- MCM4 c.*56G>A Uncertain significance ★★ same type
- MCM4 p.Ala141Gly Uncertain significance ★★ ⚠ same type
- MCM4 p.Ala436Thr Uncertain significance ★★ ⚠ same type
- MCM4 p.Ala668Thr 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/mcm4-p-ser228 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown