Is MON2 p.Ala1709Pro (c.5125G>C) pathogenic?

MON2 p.Ala1709Pro (c.5125G>C) is classified Uncertain significance in MON2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-28). AlphaMissense: likely benign (0.0942); Ultra-rare (popmax 0.0334%, amr).

How common is MON2 p.Ala1709Pro (c.5125G>C) in the general population?

MON2 p.Ala1709Pro (c.5125G>C) is ultra-rare (popmax 0.0334%, amr) (gnomAD).

What do computational predictors say about MON2 p.Ala1709Pro (c.5125G>C)?

AlphaMissense predicts likely benign (score 0.0942) — an in-silico prediction, not a clinical call.

MON2 p.Ala1709Pro

c.5125G>C · rs185959477 · VCV2459685

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0942 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0334%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0942	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -5.79	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 5.7	GERP 1.3, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 126 kb · p 2.1e-19 · regional, not allelic
Overall
CADD	23.1	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 0.0334% Admixed American · 20/59,890 alleles

Filtering AF 0.0221% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0184%

Overall 0.00525% 84/1,599,570 alleles · ultra-rare exomes 76/1,447,304 · genomes 8/152,266 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0334%	2,994
Middle Eastern	0.0167%	6,006
Remaining individualsnot grpmax-eligible	0.00648%	15,441
European (non-Finnish)	0.00479%	20,881
Ashkenazi Jewishnot grpmax-eligible	0.00343%	29,184
Finnishnot grpmax-eligible	0.00158%	63,404
African / African-American	0.00134%	74,886

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.Ala1709Pro
Coding: c.5125G>C
MANE Select: NM_015026
dbSNP: rs185959477
Type: single nucleotide variant
Location: chr12:62592720 (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.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
MON2 p.Arg1130Thr 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-ala1709pro (accessed [today's date]).

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