Is MGP p.Ser28= (c.84T>C) pathogenic?

MGP p.Ser28= (c.84T>C) is classified Conflicting classifications of pathogenicity in MGP (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-07-25). Very rare (popmax 0.00279%, afr); Associated with Keutel syndrome.

What condition is associated with MGP p.Ser28= (c.84T>C)?

MGP p.Ser28= (c.84T>C) is associated with Keutel syndrome (ClinVar).

How common is MGP p.Ser28= (c.84T>C) in the general population?

MGP p.Ser28= (c.84T>C) is very rare (popmax 0.00279%, afr) (gnomAD).

MGP p.Ser28=

c.84T>C · rs886049107 · VCV307772

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00279%, afr)

Conditions

Keutel syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.118	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP -0.015, phastCons 1
Overall
CADD	10.96	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00279% African / African-American · 2/71,582 alleles

Filtering AF 0.000464% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000174%

Overall 0.000274% 4/1,461,292 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00279%	35,791
European (non-Finnish)	0.000189%	528,173

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.Ser28=
Coding: c.84T>C
MANE Select: NM_000900
dbSNP: rs886049107
Type: single nucleotide variant
Location: chr12:14884223 (GRCh38)
Gene constraint: LOEUF 1.63 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.56 · 3 PDB
Residue 28: a modified residue (phosphoserine)

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

Disease context

Keutel syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MGP c.94+1G>A Pathogenic/Likely pathogenic ★★ same condition
MGP p.Met26Thr Uncertain significance ★★ ⚠ same condition
MGP c.-63G>A Benign ★★ same condition
MGP c.*552A>T Benign ★★ same condition
MGP p.Ala8Val Benign ★★ same condition
MGP p.Asn39His Benign/Likely benign ★★ same condition
MGP p.Asn69= Benign/Likely benign ★★ same condition
MGP p.Lys53Glu Benign/Likely benign ★★ same condition

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-ser28 (accessed [today's date]).

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