Is COL18A1 p.Val385= (c.1155C>T) pathogenic?

COL18A1 p.Val385= (c.1155C>T) is classified Likely benign in COL18A1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-08). Ultra-rare (popmax 0.05%, mid); Associated with Knobloch syndrome.

What condition is associated with COL18A1 p.Val385= (c.1155C>T)?

COL18A1 p.Val385= (c.1155C>T) is associated with Knobloch syndrome (ClinVar).

How common is COL18A1 p.Val385= (c.1155C>T) in the general population?

COL18A1 p.Val385= (c.1155C>T) is ultra-rare (popmax 0.05%, mid) (gnomAD).

COL18A1 p.Val385=

c.1155C>T · rs761020121 · VCV898135

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.05%, mid)

Conditions

Knobloch syndrome

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 -2	GERP -2
Overall
CADD	1.619	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.05% Middle Eastern · 3/5,998 alleles

Filtering AF 0.0205% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0196%

Overall 0.0205% 321/1,564,300 alleles · ultra-rare exomes 289/1,411,988 · genomes 32/152,312 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.05%	1,999
Admixed American	0.03%	3,336
Remaining individualsnot grpmax-eligible	0.0281%	3,564
European (non-Finnish)	0.0228%	4,389
African / African-American	0.0217%	4,606
Ashkenazi Jewishnot grpmax-eligible	0.0139%	7,201
South Asian	0.00235%	42,562

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.Val385=
Coding: c.1155C>T
MANE Select: NM_001379500
dbSNP: rs761020121
Type: single nucleotide variant
Location: chr21:45477899 (GRCh38)
Gene constraint: LOEUF 1.001 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 51.77 · 9 PDB
Residue 385: the fz domain

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

Disease context

Knobloch syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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.107-12131C>T Uncertain significance ★★ ⚠ same condition
COL18A1 c.1311+5G>C Uncertain significance ★★ same condition
COL18A1 c.799-3C>G Uncertain significance ★★ same condition
COL18A1 p.Ala1156Thr 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-val385 (accessed [today's date]).

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