Is MCM2 p.Arg146= (c.438C>T) pathogenic?

MCM2 p.Arg146= (c.438C>T) is classified Likely benign in MCM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-05). Absent from gnomAD v4.1.

How common is MCM2 p.Arg146= (c.438C>T) in the general population?

MCM2 p.Arg146= (c.438C>T) is absent from gnomAD v4.1 (gnomAD).

MCM2 p.Arg146=

c.438C>T · VCV3729248

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.323	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.1	GERP -4
Overall
CADD	5.078	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MCM2
Protein: p.Arg146=
Coding: c.438C>T
MANE Select: NM_004526
Type: single nucleotide variant
Location: chr3:127604921 (GRCh38)
Gene constraint: LOEUF 0.706 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.54 · 39 PDB
Residue 146: the 'interaction with kat7' region; the 'disordered' region

Full MCM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MCM2 p.Arg146Cys Uncertain significance ★ ⚠ same residue
MCM2 p.Arg146His Uncertain significance ★ ⚠ same residue
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

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-arg146 (accessed [today's date]).

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