Is COL1A1 p.Pro339= (c.1017C>T) pathogenic?

COL1A1 p.Pro339= (c.1017C>T) is classified Conflicting classifications of pathogenicity in COL1A1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-21). Very rare (popmax 0.00454%, eas); Associated with Cardiovascular phenotype.

What condition is associated with COL1A1 p.Pro339= (c.1017C>T)?

COL1A1 p.Pro339= (c.1017C>T) is associated with Cardiovascular phenotype, Caffey disease, Ehlers-Danlos syndrome, arthrochalasia type (ClinVar).

How common is COL1A1 p.Pro339= (c.1017C>T) in the general population?

COL1A1 p.Pro339= (c.1017C>T) is very rare (popmax 0.00454%, eas) (gnomAD).

COL1A1 p.Pro339=

c.1017C>T · rs543735501 · VCV890331

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00454%, eas)

Conditions

Cardiovascular phenotype

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 -1.9	GERP -3.8
Overall
CADD	9.409	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00454% East Asian · 2/44,100 alleles

Filtering AF 0.000905% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000451%

Overall 0.000815% 13/1,594,180 alleles · very rare exomes 12/1,442,030 · genomes 1/152,150 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00454%	22,050
South Asian	0.00341%	29,354
Remaining individualsnot grpmax-eligible	0.00162%	61,824
European (non-Finnish)	0.000598%	167,153

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.Pro339=
Coding: c.1017C>T
MANE Select: NM_000088
dbSNP: rs543735501
Type: single nucleotide variant
Location: chr17:50195962 (GRCh38)
Gene constraint: LOEUF 0.159 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.26 · 14 PDB
Residue 339: the 'disordered' region; the 'triple-helical region' region

Full COL1A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Caffey disease Ehlers-Danlos syndrome, arthrochalasia type osteogenesis imperfecta type 1 osteogenesis imperfecta

Similar variants

COL1A1 p.Pro339Thr 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-pro339 (accessed [today's date]).

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