Is SP7 p.Pro225= (c.675C>T) pathogenic?

SP7 p.Pro225= (c.675C>T) is classified Uncertain significance in SP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-11-01). Absent from gnomAD v4.1; Associated with osteogenesis imperfecta.

What condition is associated with SP7 p.Pro225= (c.675C>T)?

SP7 p.Pro225= (c.675C>T) is associated with osteogenesis imperfecta (ClinVar).

How common is SP7 p.Pro225= (c.675C>T) in the general population?

SP7 p.Pro225= (c.675C>T) is absent from gnomAD v4.1 (gnomAD).

How is Osteogenesis imperfecta inherited?

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

SP7 p.Pro225=

c.675C>T · rs1250981237 · VCV1702063

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 5.5	GERP -0.7, phastCons 1
Overall
CADD	9.056	PHRED · no single calibrated threshold — expert panels disagree

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: SP7
Protein: p.Pro225=
Coding: c.675C>T
MANE Select: NM_001173467
dbSNP: rs1250981237
Type: single nucleotide variant
Location: chr12:53328767 (GRCh38)
Gene constraint: LOEUF 0.808 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 52.78
Residue 225: the 'disordered' region

Full SP7 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

SP7 p.Arg267Cys Uncertain significance ★★ ⚠ same condition
SP7 p.Arg280Leu Uncertain significance ★★ ⚠ same condition
SP7 p.Cys331= Benign ★★ same condition
SP7 p.Leu288= Benign/Likely benign ★★ same condition
SP7 p.Ala285= Conflicting classifications of pathogenicity ★ same condition
SP7 p.Arg395His Conflicting classifications of pathogenicity ★ ⚠ same condition
SP7 p.Asp62Tyr Uncertain significance ★ ⚠ same condition
SP7 p.Trp167Ter Uncertain significance ★ 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/sp7-p-pro225 (accessed [today's date]).

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