Is SPARC p.Pro19Ser (c.55C>T) pathogenic?

SPARC p.Pro19Ser (c.55C>T) is classified Benign in SPARC (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.1637); Common (popmax 8.18%, afr) — too common for a highly-penetrant pathogenic allele; Associated with osteogenesis imperfecta type 17.

What condition is associated with SPARC p.Pro19Ser (c.55C>T)?

SPARC p.Pro19Ser (c.55C>T) is associated with osteogenesis imperfecta type 17, osteogenesis imperfecta (ClinVar).

What do computational predictors say about SPARC p.Pro19Ser (c.55C>T)?

AlphaMissense predicts likely benign (score 0.1637) — an in-silico prediction, not a clinical call.

SPARC p.Pro19Ser

Q: How common is SPARC p.Pro19Ser (c.55C>T) in the general population?

SPARC p.Pro19Ser (c.55C>T) is common (popmax 8.18%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.55C>T · rs6874468 · VCV1296639

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1637 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 8.18%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

osteogenesis imperfecta type 17

Computational evidence

Protein change
AlphaMissense	0.1637	likely benign
REVEL	0.167	moderately benign-leaning
SaProt	LLR -8.89	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 4.8, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 13 kb · p 9.5e-05 · 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 8.18% African / African-American · 6,132/74,986 alleles

Filtering AF 8.01% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.94%

Overall 0.431% 6,937/1,610,994 alleles · common exomes 3,343/1,458,688 · genomes 3,594/152,306 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.18%	12
Remaining individualsnot grpmax-eligible	0.58%	172
Admixed American	0.514%	195
Middle Eastern	0.264%	379
South Asian	0.0278%	3,602
European (non-Finnish)	0.00797%	12,540
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,500

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.Pro19Ser
Coding: c.55C>T
MANE Select: NM_003118
dbSNP: rs6874468
Type: single nucleotide variant
Location: chr5:151676134 (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

Also linked: osteogenesis imperfecta

Similar variants

SPARC p.Pro19= Conflicting classifications of pathogenicity ★ 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.Glu63Lys Conflicting classifications of pathogenicity ★ ⚠ 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-pro19ser (accessed [today's date]).

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