Is COL1A2 p.Pro102= (c.306T>C) pathogenic?

COL1A2 p.Pro102= (c.306T>C) is classified Likely benign in COL1A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-03). Very rare (popmax 0.00333%, amr); Associated with osteogenesis imperfecta type 1.

What condition is associated with COL1A2 p.Pro102= (c.306T>C)?

COL1A2 p.Pro102= (c.306T>C) is associated with osteogenesis imperfecta type 1, Ehlers-Danlos syndrome, classic type, 1 (ClinVar).

How common is COL1A2 p.Pro102= (c.306T>C) in the general population?

COL1A2 p.Pro102= (c.306T>C) is very rare (popmax 0.00333%, amr) (gnomAD).

COL1A2 p.Pro102=

c.306T>C · rs1255567659 · VCV2939750

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

osteogenesis imperfecta type 1

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 0.33	GERP -4.4, phastCons 1
Overall
CADD	11.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,028 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000248% 4/1,613,838 alleles · very rare exomes 4/1,461,490 · genomes 0/152,348 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,014
European (non-Finnish)	0.000169%	589,988

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.Pro102=
Coding: c.306T>C
MANE Select: NM_000089
dbSNP: rs1255567659
Type: single nucleotide variant
Location: chr7:94404582 (GRCh38)
Gene constraint: LOEUF 0.339 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 55.02 · 5 PDB
Residue 102: a modified residue (4-hydroxyproline); 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.Pro102Thr Uncertain significance ★★ ⚠ same residue
COL1A2 p.Pro102Arg Uncertain significance ★ ⚠ same residue
COL1A2 p.Pro102Ser Conflicting classifications of pathogenicity ★ ⚠ 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

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-pro102 (accessed [today's date]).

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