Is COL1A2 p.Gly331Ser (c.991G>A) pathogenic?

COL1A2 p.Gly331Ser (c.991G>A) is classified Pathogenic/Likely pathogenic in COL1A2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-16). AlphaMissense: likely pathogenic (0.8997); Absent from gnomAD v4.1; Associated with osteogenesis imperfecta type 4.

What condition is associated with COL1A2 p.Gly331Ser (c.991G>A)?

COL1A2 p.Gly331Ser (c.991G>A) is associated with osteogenesis imperfecta type 4, osteogenesis imperfecta type 1, Ehlers-Danlos syndrome, classic type, 1 (ClinVar).

How common is COL1A2 p.Gly331Ser (c.991G>A) in the general population?

COL1A2 p.Gly331Ser (c.991G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COL1A2 p.Gly331Ser (c.991G>A)?

AlphaMissense predicts likely pathogenic (score 0.8997) — an in-silico prediction, not a clinical call.

COL1A2 p.Gly331Ser

c.991G>A · rs2484708328 · VCV2946398

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8997 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

osteogenesis imperfecta type 4

Computational evidence

Protein change
AlphaMissense	0.8997	likely pathogenic ✓ concordant with ClinVar
REVEL	0.976	strongly pathogenic-leaning
SaProt	LLR -12.50	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 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 19 kb · p 2.5e-23 · regional, not allelic
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

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

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.Gly331Ser
Coding: c.991G>A
MANE Select: NM_000089
dbSNP: rs2484708328
Type: single nucleotide variant
Location: chr7:94409777 (GRCh38)
Gene constraint: LOEUF 0.339 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 55.02 · 5 PDB
Residue 331: the 'disordered' region; a UniProt-annotated variant site (in oi3)

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

Also linked: osteogenesis imperfecta type 1 Ehlers-Danlos syndrome, classic type, 1

Similar variants

COL1A2 p.Gly331= Likely benign ★★ same residue
COL1A2 p.Gly331Asp Pathogenic 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-gly331ser (accessed [today's date]).

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