Is COL1A2 p.Asp82= (c.246T>C) pathogenic?

COL1A2 p.Asp82= (c.246T>C) is classified Benign in COL1A2 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). Common (popmax 51.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with osteogenesis imperfecta type 1.

What condition is associated with COL1A2 p.Asp82= (c.246T>C)?

COL1A2 p.Asp82= (c.246T>C) is associated with osteogenesis imperfecta type 1, osteogenesis imperfecta, Ehlers-Danlos syndrome, classic type, 1 (ClinVar).

COL1A2 p.Asp82=

Q: How common is COL1A2 p.Asp82= (c.246T>C) in the general population?

COL1A2 p.Asp82= (c.246T>C) is common (popmax 51.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.246T>C · rs1800222 · VCV254955

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 51.9%, afr) — 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 1.5	GERP -0.23, phastCons 1
Overall
CADD	10.88	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 51.9% African / African-American · 37,946/73,112 alleles

Filtering AF 51.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 51.3%

Overall 14.8% 230,419/1,560,246 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	51.9%	2
East Asian	42.3%	2
Middle Eastern	17.3%	6
Remaining individualsnot grpmax-eligible	16.5%	6
Admixed American	14.8%	7
Ashkenazi Jewishnot grpmax-eligible	14.6%	7
European (non-Finnish)	11.9%	8
Finnishnot grpmax-eligible	11%	9
Amishnot grpmax-eligible	10%	10
South Asian	8.5%	12

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.Asp82=
Coding: c.246T>C
MANE Select: NM_000089
dbSNP: rs1800222
Type: single nucleotide variant
Location: chr7:94401587 (GRCh38)
Gene constraint: LOEUF 0.339 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 55.02 · 5 PDB
Residue 82: the 'disordered' region; a UniProt-annotated variant site (in edsarth2)

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 Ehlers-Danlos syndrome, classic type, 1 Ehlers-Danlos syndrome, arthrochalasia type, 2

Similar variants

COL1A2 p.Asp82Gly 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-asp82 (accessed [today's date]).

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