Is COL1A1 p.Pro451= (c.1353T>C) pathogenic?

COL1A1 p.Pro451= (c.1353T>C) is classified Uncertain significance in COL1A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-23). Ultra-rare (popmax 0.0111%, eas); Associated with osteogenesis imperfecta type 1.

What condition is associated with COL1A1 p.Pro451= (c.1353T>C)?

COL1A1 p.Pro451= (c.1353T>C) is associated with osteogenesis imperfecta type 1 (ClinVar).

How common is COL1A1 p.Pro451= (c.1353T>C) in the general population?

COL1A1 p.Pro451= (c.1353T>C) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

COL1A1 p.Pro451=

c.1353T>C · rs753764601 · VCV2895978

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

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 -9.3	GERP -3.8
Overall
CADD	0.447	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0111% East Asian · 5/44,888 alleles

Filtering AF 0.00434% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.000434% 7/1,613,296 alleles · ultra-rare exomes 6/1,461,186 · genomes 1/152,110 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,978
African / African-American	0.00267%	37,448

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: COL1A1
Protein: p.Pro451=
Coding: c.1353T>C
MANE Select: NM_000088
dbSNP: rs753764601
Type: single nucleotide variant
Location: chr17:50195047 (GRCh38)
Gene constraint: LOEUF 0.159 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.26 · 14 PDB
Residue 451: the 'disordered' region; the 'triple-helical region' region; a modified residue (4-hydroxyproline)

Full COL1A1 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

Similar variants

COL1A1 p.Pro451Ala Uncertain significance ★★ ⚠ same residue
COL1A1 c.1003-1G>A Pathogenic/Likely pathogenic ★★ same condition
COL1A1 c.103+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL1A1 c.103+2T>C Pathogenic ★★ same condition
COL1A1 c.104-1G>T Pathogenic/Likely pathogenic ★★ same condition
COL1A1 c.104-2A>G Pathogenic/Likely pathogenic ★★ same condition
COL1A1 c.1056+1G>A Pathogenic ★★ same condition
COL1A1 c.1057-1G>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/col1a1-p-pro451 (accessed [today's date]).

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