MCM5 p.Ser142=
c.426G>A · rs749822398 · VCV1660348
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00534%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.32 | acceptor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -6.3 | GERP -3 |
| Overall | ||
| CADD | 3.79 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00534%
African / African-American · 4/74,876 alleles
Filtering AF
0.00175%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00104%
Overall
0.00143%
23/1,612,734 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00534% | 18,719 |
| East Asian | 0.00223% | 44,858 |
| European (non-Finnish) | 0.00153% | 65,522 |
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
- MCM5
- Protein
- p.Ser142=
- Coding
- c.426G>A
- MANE Select
- NM_006739
- dbSNP
- rs749822398
- Type
- single nucleotide variant
- Location
- chr22:35406555 (GRCh38)
- Gene constraint
- LOEUF 0.753 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.57 · 27 PDB
- Residue 142
- an α-helix
Similar variants
- MCM5 p.Ser142Ter Uncertain significance ★ same residue
- MCM5 p.Ala160Val Uncertain significance ★★ ⚠ same type
- MCM5 p.Ala327Val Uncertain significance ★★ ⚠ same type
- MCM5 p.Ala543Thr Uncertain significance ★★ ⚠ same type
- MCM5 p.Ala620Thr Uncertain significance ★★ ⚠ same type
- MCM5 p.Arg138His Uncertain significance ★★ ⚠ same type
- MCM5 p.Arg167Cys Uncertain significance ★★ ⚠ same type
- MCM5 p.Arg167His 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/mcm5-p-ser142 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown