Is MCM2 p.Pro191Ser (c.571C>T) pathogenic?

MCM2 p.Pro191Ser (c.571C>T) is classified Uncertain significance in MCM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-13). AlphaMissense: likely pathogenic (0.874); Absent from gnomAD v4.1.

How common is MCM2 p.Pro191Ser (c.571C>T) in the general population?

MCM2 p.Pro191Ser (c.571C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MCM2 p.Pro191Ser (c.571C>T)?

AlphaMissense predicts likely pathogenic (score 0.874) — an in-silico prediction, not a clinical call.

MCM2 p.Pro191Ser

c.571C>T · rs2473277277 · VCV2756180

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.874 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.874	likely pathogenic
REVEL	0.149	moderately benign-leaning
SaProt	LLR -10.88	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 6,632 bp · p 0.67 · regional, not allelic
Overall
CADD	22.4	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

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.Pro191Ser
Coding: c.571C>T
MANE Select: NM_004526
dbSNP: rs2473277277
Type: single nucleotide variant
Location: chr3:127605054 (GRCh38)
Gene constraint: LOEUF 0.706 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.54 · 39 PDB
Residue 191: the 'interaction with kat7' region; an α-helix

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

Similar variants

MCM2 p.Pro191His 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
MCM2 p.Arg227His 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-pro191ser (accessed [today's date]).

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