Is COL1A2 p.Pro147Ser (c.439C>T) pathogenic?

COL1A2 p.Pro147Ser (c.439C>T) is classified Uncertain significance in COL1A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-18). AlphaMissense: likely benign (0.0606); Very rare (popmax 8.48e-05%, nfe); Associated with osteogenesis imperfecta type 1.

What condition is associated with COL1A2 p.Pro147Ser (c.439C>T)?

COL1A2 p.Pro147Ser (c.439C>T) is associated with osteogenesis imperfecta type 1, Ehlers-Danlos syndrome, classic type, 1 (ClinVar).

How common is COL1A2 p.Pro147Ser (c.439C>T) in the general population?

COL1A2 p.Pro147Ser (c.439C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about COL1A2 p.Pro147Ser (c.439C>T)?

AlphaMissense predicts likely benign (score 0.0606) — an in-silico prediction, not a clinical call.

COL1A2 p.Pro147Ser

c.439C>T · rs1791770915 · VCV950913

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0606 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

osteogenesis imperfecta type 1

Computational evidence

Protein change
AlphaMissense	0.0606	likely benign
REVEL	0.41	indeterminate
SaProt	LLR -8.54	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.4, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 13 kb · p 0.09 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 8.48e-05% European (non-Finnish) · 1/1,179,898 alleles

Overall 6.2e-05% 1/1,613,764 alleles · very rare exomes 1/1,461,670 · genomes 0/152,094 · joint denominator

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.Pro147Ser
Coding: c.439C>T
MANE Select: NM_000089
dbSNP: rs1791770915
Type: single nucleotide variant
Location: chr7:94405205 (GRCh38)
Gene constraint: LOEUF 0.339 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 55.02 · 5 PDB
Residue 147: 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.Pro147Arg 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-pro147ser (accessed [today's date]).

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