Is MCM7 p.Pro548Arg (c.1643C>G) pathogenic?

MCM7 p.Pro548Arg (c.1643C>G) is classified Uncertain significance in MCM7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-05). AlphaMissense: likely benign (0.1889); Absent from gnomAD v4.1.

How common is MCM7 p.Pro548Arg (c.1643C>G) in the general population?

MCM7 p.Pro548Arg (c.1643C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MCM7 p.Pro548Arg (c.1643C>G)?

AlphaMissense predicts likely benign (score 0.1889) — an in-silico prediction, not a clinical call.

MCM7 p.Pro548Arg

c.1643C>G · rs768108788 · VCV3124383

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1889 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1889	likely benign
REVEL	0.359	indeterminate
SaProt	LLR -8.78	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 8,359 bp · p 2.8e-05 · regional, not allelic
Overall
CADD	26.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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: MCM7
Protein: p.Pro548Arg
Coding: c.1643C>G
MANE Select: NM_005916
dbSNP: rs768108788
Type: single nucleotide variant
Location: chr7:100095423 (GRCh38)
Gene constraint: LOEUF 1.305 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.63 · 28 PDB
Residue 548: the mcm c-terminal aaa(+) atpase domain; the 'interaction with rad17' region; an α-helix

Full MCM7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MCM7 p.Pro548Ala Uncertain significance ★ ⚠ same residue
MCM7 p.Gly259Ala Pathogenic ★★ ⚠ same type
MCM7 p.His459= Benign ★★ same type
MCM7 p.Leu281= Likely benign ★★ same type
MCM7 p.Thr415= Benign ★★ same type
MCM7 p.Val622= Benign ★★ same type
MCM7 p.Arg527Ter Pathogenic ★ same type
MCM7 p.Gln139Ter Pathogenic ★ 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/mcm7-p-pro548arg (accessed [today's date]).

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