Is COL1A2 p.Thr16= (c.48C>T) pathogenic?

COL1A2 p.Thr16= (c.48C>T) is classified Benign/Likely benign in COL1A2 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-03-01). Rare (popmax 0.102%, amr); Associated with osteogenesis imperfecta type 1.

What condition is associated with COL1A2 p.Thr16= (c.48C>T)?

COL1A2 p.Thr16= (c.48C>T) is associated with osteogenesis imperfecta type 1, connective tissue disorder, osteogenesis imperfecta (ClinVar).

How common is COL1A2 p.Thr16= (c.48C>T) in the general population?

COL1A2 p.Thr16= (c.48C>T) is rare (popmax 0.102%, amr) (gnomAD).

COL1A2 p.Thr16=

c.48C>T · rs780687409 · VCV456841

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

rare (popmax 0.102%, 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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.18	GERP -4.4, phastCons 0.99
Overall
CADD	6.497	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.102% Admixed American · 61/59,990 alleles

Filtering AF 0.0812% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0738%

Overall 0.00582% 94/1,613,874 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.102%	983
Ashkenazi Jewishnot grpmax-eligible	0.0439%	2,277
Remaining individualsnot grpmax-eligible	0.0128%	7,810
African / African-American	0.00267%	37,440
European (non-Finnish)	0.000847%	117,998

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.Thr16=
Coding: c.48C>T
MANE Select: NM_000089
dbSNP: rs780687409
Type: single nucleotide variant
Location: chr7:94395079 (GRCh38)
Gene constraint: LOEUF 0.339 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 55.02 · 5 PDB

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: connective tissue disorder osteogenesis imperfecta Ehlers-Danlos syndrome, classic type, 1 Ehlers-Danlos syndrome, arthrochalasia type, 2

Similar variants

COL1A2 p.Thr16Ser 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.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-thr16 (accessed [today's date]).

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