Is COL15A1 p.Pro791= (c.2373G>A) pathogenic?

COL15A1 p.Pro791= (c.2373G>A) is classified Likely benign in COL15A1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-29). Ultra-rare (popmax 0.0616%, amr); Associated with COL15A1-related disorder.

What condition is associated with COL15A1 p.Pro791= (c.2373G>A)?

COL15A1 p.Pro791= (c.2373G>A) is associated with COL15A1-related disorder (ClinVar).

How common is COL15A1 p.Pro791= (c.2373G>A) in the general population?

COL15A1 p.Pro791= (c.2373G>A) is ultra-rare (popmax 0.0616%, amr) (gnomAD).

COL15A1 p.Pro791=

c.2373G>A · rs750319748 · VCV3052654

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0616%, amr)

Conditions

COL15A1-related disorder

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 -0.046	GERP -1.6, phastCons 0.41
Overall
CADD	8.498	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0616% Admixed American · 37/60,024 alleles

Filtering AF 0.0459% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0405%

Overall 0.00427% 69/1,614,164 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0616%	1,622
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0112%	8,930
East Asian	0.00669%	14,957
African / African-American	0.004%	25,011
South Asian	0.00329%	30,361
European (non-Finnish)	0.00127%	78,669

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: COL15A1
Protein: p.Pro791=
Coding: c.2373G>A
MANE Select: NM_001855
dbSNP: rs750319748
Type: single nucleotide variant
Location: chr9:99036360 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.68 · 1 PDB
Residue 791: the 'disordered' region; the 'triple-helical region 3 (col3)' region

Full COL15A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

COL15A1-related disorder

Similar variants

COL15A1 p.Pro791Ala Uncertain significance ★ ⚠ same residue
COL15A1 p.Pro791Leu Uncertain significance ★ ⚠ same residue
COL15A1 c.100+9C>A Likely benign same condition
COL15A1 c.1761+6A>G Benign same condition
COL15A1 c.1762-6T>C Benign same condition
COL15A1 c.1762-9T>C Likely benign same condition
COL15A1 c.3402+10A>G Likely benign same condition
COL15A1 c.952+9G>A Benign 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/col15a1-p-pro791 (accessed [today's date]).

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