Is SPARC p.Pro19= (c.57T>C) pathogenic?

SPARC p.Pro19= (c.57T>C) is classified Conflicting classifications of pathogenicity in SPARC (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-03-17). Very rare (popmax 0.000509%, nfe); Associated with osteogenesis imperfecta type 17.

What condition is associated with SPARC p.Pro19= (c.57T>C)?

SPARC p.Pro19= (c.57T>C) is associated with osteogenesis imperfecta type 17 (ClinVar).

How common is SPARC p.Pro19= (c.57T>C) in the general population?

SPARC p.Pro19= (c.57T>C) is very rare (popmax 0.000509%, nfe) (gnomAD).

SPARC p.Pro19=

c.57T>C · rs369337074 · VCV2958729

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 0.000509%, nfe)

Conditions

osteogenesis imperfecta type 17

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.11	GERP 1.2, phastCons 0.008
Overall
CADD	13.86	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000509% European (non-Finnish) · 6/1,178,694 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,610,832 alleles · very rare exomes 6/1,458,490 · genomes 0/152,342 · 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: SPARC
Protein: p.Pro19=
Coding: c.57T>C
MANE Select: NM_003118
dbSNP: rs369337074
Type: single nucleotide variant
Location: chr5:151676132 (GRCh38)
Gene constraint: LOEUF 0.844 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.07 · 4 PDB
Residue 19: a UniProt-annotated variant site (in)

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

Disease context

osteogenesis imperfecta type 17 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SPARC p.Pro19Ser Benign ★★ same residue
SPARC p.Gly53Arg Uncertain significance ★★ same condition
SPARC c.120+42T>C Benign ★★ same condition
SPARC c.120+8G>T Benign ★★ same condition
SPARC c.208+31C>T Benign ★★ same condition
SPARC p.Glu22= Benign ★★ same condition
SPARC c.57+1G>C Pathogenic ★ same condition
SPARC p.Arg166His Pathogenic 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/sparc-p-pro19 (accessed [today's date]).

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