Is COL18A1 p.Pro811= (c.2433G>A) pathogenic?

COL18A1 p.Pro811= (c.2433G>A) is classified Uncertain significance in COL18A1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-08-15). Very rare (popmax 0.00738%, nfe); Associated with Inborn genetic diseases.

What condition is associated with COL18A1 p.Pro811= (c.2433G>A)?

COL18A1 p.Pro811= (c.2433G>A) is associated with Inborn genetic diseases, Knobloch syndrome (ClinVar).

How common is COL18A1 p.Pro811= (c.2433G>A) in the general population?

COL18A1 p.Pro811= (c.2433G>A) is very rare (popmax 0.00738%, nfe) (gnomAD).

COL18A1 p.Pro811=

c.2433G>A · rs200147240 · VCV898258

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00738%, nfe)

Conditions

Inborn genetic diseases

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
Pangolin	Δ0.41	loss · gain 0.27 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 3.1	GERP 0.32, phastCons 1
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00738% European (non-Finnish) · 87/1,178,528 alleles

Filtering AF 0.00606% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00566%

Overall 0.0059% 95/1,609,814 alleles · very rare exomes 85/1,457,588 · genomes 10/152,226 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00738%	13,546
Remaining individualsnot grpmax-eligible	0.00642%	15,579
Finnishnot grpmax-eligible	0.0032%	31,253
East Asian	0.00223%	44,786
African / African-American	0.00134%	74,890

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: COL18A1
Protein: p.Pro811=
Coding: c.2433G>A
MANE Select: NM_001379500
dbSNP: rs200147240
Type: single nucleotide variant
Location: chr21:45494915 (GRCh38)
Gene constraint: LOEUF 1.001 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 51.77 · 9 PDB
Residue 811: the 'triple-helical region 2 (col2)' region; the 'disordered' region

Full COL18A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Knobloch syndrome

Similar variants

COL18A1 p.Pro811Leu Uncertain significance ★ ⚠ same residue
COL18A1 c.3013+3A>C Likely pathogenic ★★ same condition
COL18A1 c.3809+2T>C Pathogenic ★★ same condition
COL18A1 p.Arg790Ter Pathogenic ★★ same condition
COL18A1 c.107-11479C>A Uncertain significance ★★ ⚠ same condition
COL18A1 c.107-12077C>T Uncertain significance ★★ ⚠ same condition
COL18A1 c.107-12131C>T Uncertain significance ★★ ⚠ same condition
COL18A1 c.1311+5G>C Uncertain significance ★★ 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/col18a1-p-pro811 (accessed [today's date]).

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