Is MGP p.Pro33Ala (c.97C>G) pathogenic?

MGP p.Pro33Ala (c.97C>G) is classified Uncertain significance in MGP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-18). AlphaMissense: ambiguous (0.4618); Very rare (popmax 0.00134%, afr).

How common is MGP p.Pro33Ala (c.97C>G) in the general population?

MGP p.Pro33Ala (c.97C>G) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about MGP p.Pro33Ala (c.97C>G)?

AlphaMissense predicts ambiguous (score 0.4618) — an in-silico prediction, not a clinical call.

MGP p.Pro33Ala

c.97C>G · rs1863399284 · VCV1380649

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4618 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4618	ambiguous
REVEL	0.225	benign-leaning
SaProt	LLR -6.77	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 12	GERP 2, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 3,649 bp · p 0.62 · regional, not allelic
Overall
CADD	23.8	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 0.00134% African / African-American · 1/74,712 alleles

Overall 6.23e-05% 1/1,604,512 alleles · very rare exomes 0/1,452,392 · genomes 1/152,120 · joint denominator

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: MGP
Protein: p.Pro33Ala
Coding: c.97C>G
MANE Select: NM_000900
dbSNP: rs1863399284
Type: single nucleotide variant
Location: chr12:14883045 (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.Pro33Arg 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-pro33ala (accessed [today's date]).

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