Is COL1A1 p.Pro96= (c.288C>G) pathogenic?

COL1A1 p.Pro96= (c.288C>G) is classified Likely benign in COL1A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-14). Very rare (popmax 0.00017%, nfe); Associated with osteogenesis imperfecta type 1.

What condition is associated with COL1A1 p.Pro96= (c.288C>G)?

COL1A1 p.Pro96= (c.288C>G) is associated with osteogenesis imperfecta type 1 (ClinVar).

How common is COL1A1 p.Pro96= (c.288C>G) in the general population?

COL1A1 p.Pro96= (c.288C>G) is very rare (popmax 0.00017%, nfe) (gnomAD).

COL1A1 p.Pro96=

c.288C>G · rs1426821581 · VCV2733900

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

osteogenesis imperfecta type 1

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 -0.29	GERP -3.1, phastCons 0.003
Overall
CADD	8.579	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,740 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,612,512 alleles · very rare exomes 1/1,460,374 · genomes 1/152,138 · 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: COL1A1
Protein: p.Pro96=
Coding: c.288C>G
MANE Select: NM_000088
dbSNP: rs1426821581
Type: single nucleotide variant
Location: chr17:50199763 (GRCh38)
Gene constraint: LOEUF 0.159 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.26 · 14 PDB
Residue 96: the vwfc domain

Full COL1A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

osteogenesis imperfecta type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COL1A1 p.Pro96Leu Uncertain significance ★★ ⚠ same residue
COL1A1 c.1003-1G>A Pathogenic/Likely pathogenic ★★ same condition
COL1A1 c.103+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL1A1 c.103+2T>C Pathogenic ★★ same condition
COL1A1 c.104-1G>T Pathogenic/Likely pathogenic ★★ same condition
COL1A1 c.104-2A>G Pathogenic/Likely pathogenic ★★ same condition
COL1A1 c.1056+1G>A Pathogenic ★★ same condition
COL1A1 c.1057-1G>A 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/col1a1-p-pro96 (accessed [today's date]).

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