Is COL1A2 p.Glu443= (c.1329G>A) pathogenic?

COL1A2 p.Glu443= (c.1329G>A) is classified Likely benign in COL1A2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-08). Ultra-rare (popmax 0.047%, afr); Associated with osteogenesis imperfecta type 1.

What condition is associated with COL1A2 p.Glu443= (c.1329G>A)?

COL1A2 p.Glu443= (c.1329G>A) is associated with osteogenesis imperfecta type 1, Ehlers-Danlos syndrome, classic type, 1 (ClinVar).

How common is COL1A2 p.Glu443= (c.1329G>A) in the general population?

COL1A2 p.Glu443= (c.1329G>A) is ultra-rare (popmax 0.047%, afr) (gnomAD).

COL1A2 p.Glu443=

c.1329G>A · rs146206917 · VCV994303

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.047%, afr)

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 1.6	GERP 0.27, phastCons 1
Overall
CADD	5.924	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.047% African / African-American · 35/74,428 alleles

Filtering AF 0.0347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0305%

Overall 0.00427% 68/1,592,294 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.047%	2,127
Remaining individualsnot grpmax-eligible	0.0454%	2,201
East Asian	0.00908%	11,015
European (non-Finnish)	8.56e-05%	1,168,564

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.Glu443=
Coding: c.1329G>A
MANE Select: NM_000089
dbSNP: rs146206917
Type: single nucleotide variant
Location: chr7:94411133 (GRCh38)
Gene constraint: LOEUF 0.339 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 55.02 · 5 PDB
Residue 443: 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 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
COL1A2 c.2295+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/col1a2-p-glu443 (accessed [today's date]).

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