MCM2 p.Pro48=
c.144A>G · rs761404358 · VCV668396
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00167%, 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 -1.9 | GERP -3.9 |
| Overall | ||
| CADD | 11.44 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/59,978 alleles
Filtering AF
0.000763%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000605%
Overall
0.00105%
17/1,613,952 alleles · very rare
exomes 16/1,461,856 · genomes 1/152,096 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 59,978 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,488 |
| European (non-Finnish) | 0.00127% | 78,667 |
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.Pro48=
- Coding
- c.144A>G
- MANE Select
- NM_004526
- dbSNP
- rs761404358
- Type
- single nucleotide variant
- Location
- chr3:127599455 (GRCh38)
- Gene constraint
- LOEUF 0.706 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.54 · 39 PDB
- Residue 48
- 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-pro48 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown