Is COL1A2 p.Pro482= (c.1446A>C) pathogenic?

COL1A2 p.Pro482= (c.1446A>C) is classified Benign in COL1A2 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-04). Common (popmax 36.3%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with osteogenesis imperfecta type 1.

What condition is associated with COL1A2 p.Pro482= (c.1446A>C)?

COL1A2 p.Pro482= (c.1446A>C) is associated with osteogenesis imperfecta type 1, osteogenesis imperfecta type 2, osteogenesis imperfecta type 4 (ClinVar).

COL1A2 p.Pro482=

Q: How common is COL1A2 p.Pro482= (c.1446A>C) in the general population?

COL1A2 p.Pro482= (c.1446A>C) is common (popmax 36.3%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1446A>C · rs412777 · VCV254952

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Common

common (popmax 36.3%, nfe) — too common for a highly-penetrant pathogenic allele

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 -2.3	GERP -4.3
Overall
CADD	5.392	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 36.3% European (non-Finnish) · 428,489/1,179,748 alleles

Filtering AF 36.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 36.2%

Overall 35.5% 572,365/1,613,478 alleles · common

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	40.4%	2
European (non-Finnish)grpmax	36.3%	3
Ashkenazi Jewishnot grpmax-eligible	35.6%	3
Remaining individualsnot grpmax-eligible	35%	3
African / African-American	34.8%	3
East Asian	33.9%	3
Middle Eastern	33.8%	3
Amishnot grpmax-eligible	33.3%	3
South Asian	28.7%	3
Admixed American	26.5%	4

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro482=
Coding: c.1446A>C
MANE Select: NM_000089
dbSNP: rs412777
Type: single nucleotide variant
Location: chr7:94412625 (GRCh38)
Gene constraint: LOEUF 0.339 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 55.02 · 5 PDB
Residue 482: 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: osteogenesis imperfecta type 2 osteogenesis imperfecta type 4 osteogenesis imperfecta type 3 osteogenesis imperfecta Ehlers-Danlos syndrome, classic type, 1 Ehlers-Danlos syndrome, arthrochalasia type, 2

Similar variants

COL1A2 p.Pro482Ser Uncertain significance ★ ⚠ same residue
COL1A2 p.Pro482Thr Uncertain significance ★ ⚠ same residue
COL1A2 p.Pro482His Uncertain significance ★ 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.1972-1G>T 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-pro482 (accessed [today's date]).

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