MCM2 p.Arg82=
c.246C>T · rs186022338 · VCV1571289
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0175%, 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 -4.1 | GERP -4 |
| Overall | ||
| CADD | 7.821 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0175%
Middle Eastern · 1/5,698 alleles
Filtering AF
0.0146%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0139%
Overall
0.013%
210/1,613,002 alleles · ultra-rare
exomes 204/1,460,662 · genomes 6/152,340 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0175% | 5,698 |
| European (non-Finnish) | 0.0165% | 6,051 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,919 |
| Admixed American | 0.00666% | 15,006 |
| African / African-American | 0.00267% | 37,521 |
| East Asian | 0.00223% | 44,876 |
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.Arg82=
- Coding
- c.246C>T
- MANE Select
- NM_004526
- dbSNP
- rs186022338
- Type
- single nucleotide variant
- Location
- chr3:127604617 (GRCh38)
- Gene constraint
- LOEUF 0.706 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.54 · 39 PDB
- Residue 82
- the 'interaction with kat7' region; the 'interaction with dnjc9' region
Similar variants
- MCM2 p.Arg82His Uncertain significance ★ ⚠ same residue
- 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
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-arg82 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown