Is MON2 p.Arg860= (c.2578A>C) pathogenic?

MON2 p.Arg860= (c.2578A>C) is classified Likely benign in MON2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-24). Very rare (popmax 0.000171%, nfe).

How common is MON2 p.Arg860= (c.2578A>C) in the general population?

MON2 p.Arg860= (c.2578A>C) is very rare (popmax 0.000171%, nfe) (gnomAD).

MON2 p.Arg860=

c.2578A>C · VCV4109550

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000171%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.4, phastCons 1
Overall
CADD	14.15	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000171% European (non-Finnish) · 2/1,168,730 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000126% 2/1,592,464 alleles · very rare exomes 2/1,440,212 · genomes 0/152,252 · joint denominator

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: MON2
Protein: p.Arg860=
Coding: c.2578A>C
MANE Select: NM_015026
Type: single nucleotide variant
Location: chr12:62546897 (GRCh38)
Gene constraint: LOEUF 0.426 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.50

Full MON2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MON2 p.Ala1282Gly Uncertain significance ★ ⚠ same type
MON2 p.Ala1334Ser Uncertain significance ★ ⚠ same type
MON2 p.Ala1366Val Uncertain significance ★ ⚠ same type
MON2 p.Ala1709Pro Uncertain significance ★ ⚠ same type
MON2 p.Ala590Thr Uncertain significance ★ ⚠ same type
MON2 p.Ala687Val Uncertain significance ★ ⚠ same type
MON2 p.Arg1010Gln Uncertain significance ★ ⚠ same type
MON2 p.Arg1037Cys 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/mon2-p-arg860 (accessed [today's date]).

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