MCM2 p.Ser468=
c.1404C>G · rs140620010 · VCV514697
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.351%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.025 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 1 | GERP -1.9, phastCons 1 |
| Overall | ||
| CADD | 8.638 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.351%
African / African-American · 263/75,034 alleles
Filtering AF
0.316%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.302%
Overall
0.019%
306/1,614,102 alleles · rare
exomes 153/1,461,826 · genomes 153/152,276 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.351% | 285 |
| Remaining individualsnot grpmax-eligible | 0.0304% | 3,290 |
| Admixed American | 0.03% | 3,334 |
| European (non-Finnish) | 0.000508% | 196,670 |
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
- MCM2
- Protein
- p.Ser468=
- Coding
- c.1404C>G
- MANE Select
- NM_004526
- dbSNP
- rs140620010
- Type
- single nucleotide variant
- Location
- chr3:127608999 (GRCh38)
- Gene constraint
- LOEUF 0.706 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.54 · 39 PDB
- Residue 468
- the mcm c-terminal aaa(+) atpase domain; an α-helix
Similar variants
- MCM2 p.Ala148Thr Uncertain significance ★★ ⚠ same type
- MCM2 p.Ala2Glu Uncertain significance ★★ ⚠ same type
- MCM2 p.Ala400Thr Uncertain significance ★★ ⚠ same type
- MCM2 p.Arg126Gln Uncertain significance ★★ ⚠ same type
- MCM2 p.Arg149His Uncertain significance ★★ ⚠ same type
- MCM2 p.Arg152His Uncertain significance ★★ ⚠ same type
- MCM2 p.Arg227His Uncertain significance ★★ ⚠ same type
- MCM2 p.Arg284Cys 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/mcm2-p-ser468 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown