Is MGP p.Arg99Pro (c.296G>C) pathogenic?

MGP p.Arg99Pro (c.296G>C) is classified Uncertain significance in MGP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-13). AlphaMissense: likely benign (0.1217); Absent from gnomAD v4.1.

How common is MGP p.Arg99Pro (c.296G>C) in the general population?

MGP p.Arg99Pro (c.296G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MGP p.Arg99Pro (c.296G>C)?

AlphaMissense predicts likely benign (score 0.1217) — an in-silico prediction, not a clinical call.

MGP p.Arg99Pro

c.296G>C · VCV3646796

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1217 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1217	likely benign
REVEL	0.266	benign-leaning
SaProt	LLR -8.59	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 2.8	GERP 1.1, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 3,649 bp · p 0.62 · regional, not allelic
Overall
CADD	23.3	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

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: MGP
Protein: p.Arg99Pro
Coding: c.296G>C
MANE Select: NM_000900
Type: single nucleotide variant
Location: chr12:14882155 (GRCh38)
Gene constraint: LOEUF 1.63 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.56 · 3 PDB

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

Similar variants

MGP p.Arg99His Uncertain significance ★ ⚠ same residue
MGP c.94+1G>A Pathogenic/Likely pathogenic ★★ same type
MGP c.94+5G>A Uncertain significance ★★ same type
MGP p.Arg61His Uncertain significance ★★ ⚠ same type
MGP p.Gln47Glu Uncertain significance ★★ ⚠ same type
MGP p.Met26Thr Uncertain significance ★★ ⚠ same type
MGP p.Tyr76His Uncertain significance ★★ ⚠ same type
MGP c.171-67T>A Likely benign ★★ 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/mgp-p-arg99pro (accessed [today's date]).

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