MCM3AP p.Pro413=
c.1239G>A · rs139966669 · VCV707837
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0362%, mid)
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 0.045 | GERP -3.2 |
| Overall | ||
| CADD | 4.036 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0362%
Middle Eastern · 2/5,526 alleles
Filtering AF
0.0296%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0285%
Overall
0.0276%
445/1,613,114 alleles · ultra-rare
exomes 412/1,460,968 · genomes 33/152,146 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0362% | 2,763 |
| European (non-Finnish) | 0.0323% | 3,097 |
| South Asian | 0.0275% | 3,642 |
| Finnishnot grpmax-eligible | 0.025% | 4,002 |
| Admixed American | 0.0183% | 5,453 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0101% | 9,869 |
| Remaining individualsnot grpmax-eligible | 0.00801% | 12,482 |
| African / African-American | 0.00267% | 37,442 |
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
- MCM3AP
- Protein
- p.Pro413=
- Coding
- c.1239G>A
- MANE Select
- NM_003906
- dbSNP
- rs139966669
- Type
- single nucleotide variant
- Location
- chr21:46283819 (GRCh38)
- Gene constraint
- LOEUF 0.769 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 65.83 · 7 PDB
- Residue 413
- a UniProt-annotated variant site (in); the 'disordered' region
Similar variants
- MCM3AP p.Pro413Leu Benign ★★ same residue
- MCM3AP c.3933-1G>T Likely pathogenic ★★ same type
- MCM3AP c.1443+4A>G Uncertain significance ★★ same type
- MCM3AP p.Ala1102Ser Uncertain significance ★★ ⚠ same type
- MCM3AP p.Ala1104Val Uncertain significance ★★ ⚠ same type
- MCM3AP p.Ala1117Val Uncertain significance ★★ ⚠ same type
- MCM3AP p.Ala1283Thr Uncertain significance ★★ ⚠ same type
- MCM3AP p.Ala1495Val 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/mcm3ap-p-pro413 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown