Is COL1A2 p.Pro989= (c.2967T>C) pathogenic?

COL1A2 p.Pro989= (c.2967T>C) is classified Benign/Likely benign in COL1A2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-06). Rare (popmax 0.109%, eas); Associated with osteogenesis imperfecta type 1.

What condition is associated with COL1A2 p.Pro989= (c.2967T>C)?

COL1A2 p.Pro989= (c.2967T>C) is associated with osteogenesis imperfecta type 1, Ehlers-Danlos syndrome, classic type, 1 (ClinVar).

How common is COL1A2 p.Pro989= (c.2967T>C) in the general population?

COL1A2 p.Pro989= (c.2967T>C) is rare (popmax 0.109%, eas) (gnomAD).

COL1A2 p.Pro989=

c.2967T>C · rs201760437 · VCV710887

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.109%, eas)

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 -7.7	GERP -4.1
Overall
CADD	1.219	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.109% East Asian · 49/44,886 alleles

Filtering AF 0.0848% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0761%

Overall 0.00316% 51/1,614,216 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.109%	916
Remaining individualsnot grpmax-eligible	0.0016%	62,510
European (non-Finnish)	8.47e-05%	1,180,036

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: COL1A2
Protein: p.Pro989=
Coding: c.2967T>C
MANE Select: NM_000089
dbSNP: rs201760437
Type: single nucleotide variant
Location: chr7:94426021 (GRCh38)
Gene constraint: LOEUF 0.339 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 55.02 · 5 PDB
Residue 989: a UniProt-annotated variant site (in oi4); the 'disordered' region

Full COL1A2 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

Also linked: Ehlers-Danlos syndrome, classic type, 1

Similar variants

COL1A2 p.Pro989_Gly991dup Pathogenic/Likely pathogenic ★★ same residue
COL1A2 c.1197+5G>A Pathogenic ★★ same condition
COL1A2 c.1503+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL1A2 c.1503+1G>C Pathogenic ★★ same condition
COL1A2 c.1557+3A>G Pathogenic ★★ same condition
COL1A2 c.2026-2A>G Pathogenic/Likely pathogenic ★★ same condition
COL1A2 c.2133+6T>A Pathogenic ★★ same condition
COL1A2 c.226-2A>G Pathogenic/Likely 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/col1a2-p-pro989 (accessed [today's date]).

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