Is COL1A2 p.Arg1053= (c.3159G>A) pathogenic?

COL1A2 p.Arg1053= (c.3159G>A) is classified Uncertain significance in COL1A2 (ClinVar, Single submitter, 3 submitters; last evaluated 2020-03-05). Absent from gnomAD v4.1; Associated with osteogenesis imperfecta type 4.

What condition is associated with COL1A2 p.Arg1053= (c.3159G>A)?

COL1A2 p.Arg1053= (c.3159G>A) is associated with osteogenesis imperfecta type 4 (ClinVar).

How common is COL1A2 p.Arg1053= (c.3159G>A) in the general population?

COL1A2 p.Arg1053= (c.3159G>A) is absent from gnomAD v4.1 (gnomAD).

COL1A2 p.Arg1053=

c.3159G>A · rs2484737404 · VCV1806466

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

osteogenesis imperfecta type 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.56	donor loss · deltas
Pangolin	Δ0.57	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Overall
CADD	21.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COL1A2
Protein: p.Arg1053=
Coding: c.3159G>A
MANE Select: NM_000089
dbSNP: rs2484737404
Type: single nucleotide variant
Location: chr7:94427061 (GRCh38)
Gene constraint: LOEUF 0.339 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 55.02 · 5 PDB
Residue 1053: the 'disordered' region

Full COL1A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

osteogenesis imperfecta type 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COL1A2 p.Arg1053Gly Uncertain significance ★★ ⚠ same residue
COL1A2 p.Arg1053Ser Uncertain significance ★ ⚠ same residue
COL1A2 c.1197+5G>A Pathogenic ★★ same condition
COL1A2 c.1557+3A>G Pathogenic ★★ same condition
COL1A2 c.2133+6T>A Pathogenic ★★ same condition
COL1A2 c.2835+1G>A Pathogenic ★★ same condition
COL1A2 c.433-2A>C Pathogenic/Likely pathogenic ★★ same condition
COL1A2 p.Ala1119Thr 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-arg1053 (accessed [today's date]).

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