Is MBTPS2 p.Pro153= (c.459C>T) pathogenic?

MBTPS2 p.Pro153= (c.459C>T) is classified Benign/Likely benign in MBTPS2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-11-12). Low-frequency (popmax 2.37%, sas); Associated with osteogenesis imperfecta.

What condition is associated with MBTPS2 p.Pro153= (c.459C>T)?

MBTPS2 p.Pro153= (c.459C>T) is associated with osteogenesis imperfecta (ClinVar).

How common is MBTPS2 p.Pro153= (c.459C>T) in the general population?

MBTPS2 p.Pro153= (c.459C>T) is low-frequency (popmax 2.37%, sas) (gnomAD).

How is Osteogenesis imperfecta inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

MBTPS2 p.Pro153=

c.459C>T · rs371946947 · VCV749284

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.37%, sas)

Conditions

osteogenesis imperfecta

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.6	GERP -4.8
Overall
CADD	2.287	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.37% South Asian · 1,342/56,547 alleles

Filtering AF 2.27% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.23%

Overall 0.119% 1,426/1,202,135 alleles · low-frequency exomes 1,348/1,091,067 · genomes 78/111,068 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	2.37%	42
Middle Eastern	0.138%	723
Remaining individualsnot grpmax-eligible	0.133%	752
African / African-American	0.0088%	11,361
East Asian	0.00297%	33,692
Admixed American	0.00219%	45,616
European (non-Finnish)	0.0009%	111,081

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: MBTPS2
Protein: p.Pro153=
Coding: c.459C>T
MANE Select: NM_015884
dbSNP: rs371946947
Type: single nucleotide variant
Location: chrX:21851529 (GRCh38)
Structure: AlphaFold pLDDT 87.78

Full MBTPS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

osteogenesis imperfecta — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Osteogenesis imperfecta (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: All ages
Prevalence: 1-5 / 10 000 (Worldwide)

Similar variants

MBTPS2 p.His413Tyr Benign/Likely benign ★★ same condition
MBTPS2 p.Ser136= Benign/Likely benign ★★ same condition
MBTPS2 c.671-10C>G Conflicting classifications of pathogenicity ★ same condition
MBTPS2 c.970+5G>A Pathogenic ★★ same type
MBTPS2 p.Arg429His Pathogenic ★★ same type
MBTPS2 p.Asn508Ser Pathogenic ★★ same type
MBTPS2 p.Ala507Val Uncertain significance ★★ same type
MBTPS2 p.Arg327Gln 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/mbtps2-p-pro153 (accessed [today's date]).

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