Is COL1A2 p.Arg327Cys (c.979C>T) pathogenic?

COL1A2 p.Arg327Cys (c.979C>T) is classified Uncertain significance in COL1A2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-08-26). AlphaMissense: likely pathogenic (0.7103); Ultra-rare (popmax 0.0233%, amr); Associated with osteogenesis imperfecta type 1.

What condition is associated with COL1A2 p.Arg327Cys (c.979C>T)?

COL1A2 p.Arg327Cys (c.979C>T) is associated with osteogenesis imperfecta type 1, Ehlers-Danlos syndrome, classic type, 1 (ClinVar).

How common is COL1A2 p.Arg327Cys (c.979C>T) in the general population?

COL1A2 p.Arg327Cys (c.979C>T) is ultra-rare (popmax 0.0233%, amr) (gnomAD).

What do computational predictors say about COL1A2 p.Arg327Cys (c.979C>T)?

AlphaMissense predicts likely pathogenic (score 0.7103) — an in-silico prediction, not a clinical call.

COL1A2 p.Arg327Cys

c.979C>T · rs760682336 · VCV2068285

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7103 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0233%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

osteogenesis imperfecta type 1

Computational evidence

Protein change
AlphaMissense	0.7103	likely pathogenic
REVEL	0.721	pathogenic-leaning
SaProt	LLR -13.27	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 19 kb · p 2.5e-23 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0233% Admixed American · 14/60,002 alleles

Filtering AF 0.0141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0112%

Overall 0.00155% 25/1,614,012 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0233%	4,286
East Asian	0.00223%	44,870
Remaining individualsnot grpmax-eligible	0.0016%	62,488
African / African-American	0.00134%	74,904
European (non-Finnish)	0.000678%	147,504

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.Arg327Cys
Coding: c.979C>T
MANE Select: NM_000089
dbSNP: rs760682336
Type: single nucleotide variant
Location: chr7:94409765 (GRCh38)
Gene constraint: LOEUF 0.339 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 55.02 · 5 PDB
Residue 327: 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 p.Arg327= Benign/Likely benign ★★ same residue
COL1A2 p.Arg327His Conflicting classifications of pathogenicity ★ ⚠ 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

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-arg327cys (accessed [today's date]).

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