Is MCM2 p.Asp164= (c.492C>T) pathogenic?

MCM2 p.Asp164= (c.492C>T) is classified Benign in MCM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-01). Rare (popmax 0.256%, sas).

How common is MCM2 p.Asp164= (c.492C>T) in the general population?

MCM2 p.Asp164= (c.492C>T) is rare (popmax 0.256%, sas) (gnomAD).

MCM2 p.Asp164=

c.492C>T · rs562643137 · VCV2045715

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.256%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.031	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -16	GERP -3.8
Overall
CADD	0.885	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.256% South Asian · 233/91,082 alleles

Filtering AF 0.229% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.218%

Overall 0.0169% 272/1,613,818 alleles · rare exomes 260/1,461,558 · genomes 12/152,260 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.256%	391
Remaining individualsnot grpmax-eligible	0.0224%	4,463
African / African-American	0.00666%	15,008
East Asian	0.00446%	22,441
European (non-Finnish)	0.00153%	65,546

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: MCM2
Protein: p.Asp164=
Coding: c.492C>T
MANE Select: NM_004526
dbSNP: rs562643137
Type: single nucleotide variant
Location: chr3:127604975 (GRCh38)
Gene constraint: LOEUF 0.706 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.54 · 39 PDB
Residue 164: 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.Asp164_Glu166dup Conflicting classifications of pathogenicity ★ 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-asp164 (accessed [today's date]).

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