MCM4 p.Arg718=
c.2154G>A · rs1312065989 · VCV2078690
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00136%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.24 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.3 | GERP -0.33, phastCons 1 |
| Overall | ||
| CADD | 7.513 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00136%
European (non-Finnish) · 16/1,179,992 alleles
Filtering AF
0.000803%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00065%
Overall
0.00105%
17/1,614,184 alleles · very rare
exomes 17/1,461,824 · genomes 0/152,360 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00136% | 73,750 |
| South Asian | 0.0011% | 91,088 |
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
- MCM4
- Protein
- p.Arg718=
- Coding
- c.2154G>A
- MANE Select
- NM_182746
- dbSNP
- rs1312065989
- Type
- single nucleotide variant
- Location
- chr8:47974751 (GRCh38)
- Gene constraint
- LOEUF 0.806 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.25 · 28 PDB
- Residue 718
- an α-helix; the mcm c-terminal aaa(+) atpase domain
Similar variants
- MCM4 c.71-2A>G Pathogenic ★★ same type
- MCM4 c.-74C>T Uncertain significance ★★ same type
- MCM4 c.*56G>A Uncertain significance ★★ same type
- MCM4 p.Ala141Gly Uncertain significance ★★ ⚠ same type
- MCM4 p.Ala436Thr Uncertain significance ★★ ⚠ same type
- MCM4 p.Ala668Thr Uncertain significance ★★ ⚠ same type
- MCM4 p.Ala685Val Uncertain significance ★★ ⚠ same type
- MCM4 p.Ala694Thr 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/mcm4-p-arg718 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown