MCM2 p.Ser53=
c.159C>T · rs572319263 · VCV1342828
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0834%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.8 | GERP -3.9 |
| Overall | ||
| CADD | 9.054 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0834%
Admixed American · 50/59,986 alleles
Filtering AF
0.0649%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0584%
Overall
0.00545%
88/1,613,976 alleles · ultra-rare
exomes 81/1,461,858 · genomes 7/152,118 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0834% | 1,200 |
| Middle Eastern | 0.0164% | 6,084 |
| South Asian | 0.0121% | 8,281 |
| East Asian | 0.0111% | 8,979 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,242 |
| Finnishnot grpmax-eligible | 0.00156% | 63,996 |
| European (non-Finnish) | 0.00153% | 65,557 |
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.Ser53=
- Coding
- c.159C>T
- MANE Select
- NM_004526
- dbSNP
- rs572319263
- Type
- single nucleotide variant
- Location
- chr3:127599470 (GRCh38)
- Gene constraint
- LOEUF 0.706 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.54 · 39 PDB
- Residue 53
- a modified residue (phosphoserine; by cdc7); the 'disordered' region; the 'interaction with kat7' region
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-ser53 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown