MCM2 p.Asp672=
c.2016C>T · VCV4749474
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0324%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.449 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -4.7 | GERP -4.2 |
| Overall | ||
| CADD | 6.186 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0324%
Admixed American · 19/58,702 alleles
Filtering AF
0.0211%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0175%
Overall
0.00421%
67/1,592,926 alleles · ultra-rare
exomes 61/1,440,730 · genomes 6/152,196 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0324% | 3,090 |
| African / African-American | 0.00536% | 18,646 |
| European (non-Finnish) | 0.0036% | 27,784 |
| Remaining individualsnot grpmax-eligible | 0.00162% | 61,570 |
| South Asian | 0.00113% | 88,594 |
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.Asp672=
- Coding
- c.2016C>T
- MANE Select
- NM_004526
- Type
- single nucleotide variant
- Location
- chr3:127619029 (GRCh38)
- Gene constraint
- LOEUF 0.706 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.54 · 39 PDB
- Residue 672
- an α-helix; 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-asp672 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown