Is COL18A1 p.Pro620fs (c.1857dup) pathogenic?

COL18A1 p.Pro620fs (c.1857dup) is classified Pathogenic in COL18A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-28). Very rare (popmax 0.0011%, sas).

How common is COL18A1 p.Pro620fs (c.1857dup) in the general population?

COL18A1 p.Pro620fs (c.1857dup) is very rare (popmax 0.0011%, sas) (gnomAD).

COL18A1 p.Pro620fs

c.1857dup · rs2517661534 · VCV2699523

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 17 of 42
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -8	GERP -2.2

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,084 alleles

Overall 0.000124% 2/1,613,040 alleles · very rare exomes 2/1,460,748 · genomes 0/152,292 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00159%	63,072
South Asiangrpmax	0.0011%	91,084

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro620fs
Coding: c.1857dup
MANE Select: NM_001379500
dbSNP: rs2517661534
Type: Duplication
Location: chr21:45487464 (GRCh38)
Gene constraint: LOEUF 1.001 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 51.77 · 9 PDB
Residue 620: the laminin g-like domain

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

Similar variants

COL18A1 p.Pro620= Likely benign ★ same residue
COL18A1 p.Ala211fs Pathogenic/Likely pathogenic ★★ same type
COL18A1 p.Arg332fs Pathogenic/Likely pathogenic ★★ same type
COL18A1 p.Gln230fs Pathogenic/Likely pathogenic ★★ same type
COL18A1 p.Glu926fs Pathogenic/Likely pathogenic ★★ same type
COL18A1 p.Gly1019fs Pathogenic/Likely pathogenic ★★ same type
COL18A1 p.Gly598fs Pathogenic/Likely pathogenic ★★ same type
COL18A1 p.Gly977fs Pathogenic ★★ same type

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-pro620fs (accessed [today's date]).

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