MCM2 p.Asp668=
c.2004C>T · rs778483309 · VCV1317287
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.065%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.05 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 0.52 | GERP -2.8, phastCons 1 |
| Overall | ||
| CADD | 7.675 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.065%
Admixed American · 39/59,992 alleles
Filtering AF
0.0488%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0432%
Overall
0.00242%
39/1,613,640 alleles · ultra-rare
exomes 38/1,461,484 · genomes 1/152,156 · joint denominator
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.Asp668=
- Coding
- c.2004C>T
- MANE Select
- NM_004526
- dbSNP
- rs778483309
- Type
- single nucleotide variant
- Location
- chr3:127618072 (GRCh38)
- Gene constraint
- LOEUF 0.706 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.54 · 39 PDB
- Residue 668
- the mcm c-terminal aaa(+) atpase domain
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-asp668 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown