Is MON2 p.Ala687Val (c.2060C>T) pathogenic?

MON2 p.Ala687Val (c.2060C>T) is classified Uncertain significance in MON2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-22). AlphaMissense: likely pathogenic (0.8399); Very rare (popmax 0.00446%, eas).

How common is MON2 p.Ala687Val (c.2060C>T) in the general population?

MON2 p.Ala687Val (c.2060C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about MON2 p.Ala687Val (c.2060C>T)?

AlphaMissense predicts likely pathogenic (score 0.8399) — an in-silico prediction, not a clinical call.

MON2 p.Ala687Val

c.2060C>T · VCV3912445

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8399 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8399	likely pathogenic
REVEL	0.599	indeterminate
SaProt	LLR -7.83	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.8, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 126 kb · p 2.1e-19 · regional, not allelic
Overall
CADD	27.9	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

Grpmax group 0.00446% East Asian · 2/44,828 alleles

Filtering AF 0.00074% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000868% 14/1,613,086 alleles · very rare exomes 12/1,460,930 · genomes 2/152,156 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,414
Admixed American	0.00167%	59,784
African / African-American	0.00134%	74,876
European (non-Finnish)	0.000848%	117,965

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.Ala687Val
Coding: c.2060C>T
MANE Select: NM_015026
Type: single nucleotide variant
Location: chr12:62537648 (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.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-ala687val (accessed [today's date]).

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