Is MON2 p.Ser1305Arg (c.3915T>A) pathogenic?

MON2 p.Ser1305Arg (c.3915T>A) is classified Uncertain significance in MON2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-07). AlphaMissense: ambiguous (0.3935); Absent from gnomAD v4.1.

How common is MON2 p.Ser1305Arg (c.3915T>A) in the general population?

MON2 p.Ser1305Arg (c.3915T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MON2 p.Ser1305Arg (c.3915T>A)?

AlphaMissense predicts ambiguous (score 0.3935) — an in-silico prediction, not a clinical call.

MON2 p.Ser1305Arg

c.3915T>A · VCV3874003

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3935 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3935	ambiguous
REVEL	0.124	moderately benign-leaning
SaProt	LLR -6.17	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.064	GERP -3.1, phastCons 0.88
Regional constraint	o/e 0.80	unconstrained · MANE · 126 kb · p 2.1e-19 · regional, not allelic
Overall
CADD	16.21	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MON2
Protein: p.Ser1305Arg
Coding: c.3915T>A
MANE Select: NM_015026
Type: single nucleotide variant
Location: chr12:62560996 (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-ser1305arg (accessed [today's date]).

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