Is COL18A1 p.Ser617= (c.1851C>T) pathogenic?

COL18A1 p.Ser617= (c.1851C>T) is classified Likely benign in COL18A1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-09-14). Ultra-rare (popmax 0.0259%, nfe); Associated with Inborn genetic diseases.

What condition is associated with COL18A1 p.Ser617= (c.1851C>T)?

COL18A1 p.Ser617= (c.1851C>T) is associated with Inborn genetic diseases (ClinVar).

How common is COL18A1 p.Ser617= (c.1851C>T) in the general population?

COL18A1 p.Ser617= (c.1851C>T) is ultra-rare (popmax 0.0259%, nfe) (gnomAD).

COL18A1 p.Ser617=

c.1851C>T · rs376114537 · VCV1155321

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0259%, 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
Constraint at this position
Conservation	phyloP -8	GERP -2.2
Overall
CADD	7.28	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0259% European (non-Finnish) · 306/1,179,990 alleles

Filtering AF 0.0235% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0226%

Overall 0.0201% 325/1,612,930 alleles · ultra-rare exomes 307/1,460,756 · genomes 18/152,174 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0259%	3,856
African / African-American	0.012%	8,324
Remaining individualsnot grpmax-eligible	0.008%	12,492
Admixed American	0.00667%	15,002
South Asian	0.0011%	91,088

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.Ser617=
Coding: c.1851C>T
MANE Select: NM_001379500
dbSNP: rs376114537
Type: single nucleotide variant
Location: chr21:45487464 (GRCh38)
Gene constraint: LOEUF 1.001 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 51.77 · 9 PDB
Residue 617: the laminin g-like domain

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

Similar variants

COL18A1 p.Ser617Pro Uncertain significance ★ ⚠ same residue
COL18A1 c.107-12077C>T Uncertain significance ★★ ⚠ same condition
COL18A1 p.Ala1123Thr Uncertain significance ★★ ⚠ same condition
COL18A1 p.Ala115Val Uncertain significance ★★ ⚠ same condition
COL18A1 p.Ala157Thr Uncertain significance ★★ ⚠ same condition
COL18A1 p.Ala208Val Uncertain significance ★★ ⚠ same condition
COL18A1 p.Ala378Thr Uncertain significance ★★ ⚠ same condition
COL18A1 p.Ala519Thr 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-ser617 (accessed [today's date]).

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