Is MCM7 p.Arg147Pro (c.440G>C) pathogenic?

MCM7 p.Arg147Pro (c.440G>C) is classified Uncertain significance in MCM7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-11). AlphaMissense: likely pathogenic (0.7367); Very rare (popmax 0.00659%, sas).

How common is MCM7 p.Arg147Pro (c.440G>C) in the general population?

MCM7 p.Arg147Pro (c.440G>C) is very rare (popmax 0.00659%, sas) (gnomAD).

What do computational predictors say about MCM7 p.Arg147Pro (c.440G>C)?

AlphaMissense predicts likely pathogenic (score 0.7367) — an in-silico prediction, not a clinical call.

MCM7 p.Arg147Pro

c.440G>C · VCV4105176

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7367 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7367	likely pathogenic
REVEL	0.12	moderately benign-leaning
SaProt	LLR -9.63	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4	GERP 1.8, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 8,359 bp · p 2.8e-05 · regional, not allelic
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00659% South Asian · 6/91,090 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.00242% 39/1,613,966 alleles · very rare exomes 35/1,461,892 · genomes 4/152,074 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00659%	15,182
Remaining individualsnot grpmax-eligible	0.0048%	20,829
European (non-Finnish)	0.00237%	42,144
Finnishnot grpmax-eligible	0.00156%	64,020
African / African-American	0.00134%	74,858

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: MCM7
Protein: p.Arg147Pro
Coding: c.440G>C
MANE Select: NM_005916
Type: single nucleotide variant
Location: chr7:100099165 (GRCh38)
Gene constraint: LOEUF 1.305 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.63 · 28 PDB

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

Similar variants

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
MCM7 p.Gln45Ter 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-arg147pro (accessed [today's date]).

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