Is MCM5 p.Leu730= (c.2190C>T) pathogenic?

MCM5 p.Leu730= (c.2190C>T) is classified Likely benign in MCM5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-23). No allele count reported in gnomAD v4.1 (AN 1,548,876).

How common is MCM5 p.Leu730= (c.2190C>T) in the general population?

MCM5 p.Leu730= (c.2190C>T) is no allele count reported in gnomAD v4.1 (AN 1,548,876) (gnomAD).

MCM5 p.Leu730=

c.2190C>T · VCV3723658

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,548,876)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.41	GERP -1.7, phastCons 0.99
Overall
CADD	7.409	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,548,876). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MCM5
Protein: p.Leu730=
Coding: c.2190C>T
MANE Select: NM_006739
Type: single nucleotide variant
Location: chr22:35424240 (GRCh38)
Gene constraint: LOEUF 0.753 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.57 · 27 PDB
Residue 730: an α-helix

Full MCM5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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
MCM5 p.Arg176Cys 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-leu730 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown