Is MON2 p.Met485Val (c.1453A>G) pathogenic?

MON2 p.Met485Val (c.1453A>G) is classified Uncertain significance in MON2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-18). AlphaMissense: likely benign (0.1577); Very rare (popmax 0.00878%, sas).

How common is MON2 p.Met485Val (c.1453A>G) in the general population?

MON2 p.Met485Val (c.1453A>G) is very rare (popmax 0.00878%, sas) (gnomAD).

What do computational predictors say about MON2 p.Met485Val (c.1453A>G)?

AlphaMissense predicts likely benign (score 0.1577) — an in-silico prediction, not a clinical call.

MON2 p.Met485Val

c.1453A>G · VCV3912439

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1577 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00878%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1577	likely benign
REVEL	0.269	benign-leaning
SaProt	LLR -2.70	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.3, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 126 kb · p 2.1e-19 · regional, not allelic
Overall
CADD	23.0	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

Grpmax group 0.00878% South Asian · 8/91,094 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.000682% 11/1,614,048 alleles · very rare exomes 9/1,461,846 · genomes 2/152,202 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00878%	11,387
Finnishnot grpmax-eligible	0.00156%	64,030
African / African-American	0.00133%	74,934
European (non-Finnish)	8.47e-05%	1,180,025

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.Met485Val
Coding: c.1453A>G
MANE Select: NM_015026
Type: single nucleotide variant
Location: chr12:62532490 (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-met485val (accessed [today's date]).

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