Is COL18A1 p.Gly485Val (c.1454G>T) pathogenic?

COL18A1 p.Gly485Val (c.1454G>T) is classified Uncertain significance in COL18A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-27). AlphaMissense: likely benign (0.2898); Very rare (popmax 0.000932%, nfe).

How common is COL18A1 p.Gly485Val (c.1454G>T) in the general population?

COL18A1 p.Gly485Val (c.1454G>T) is very rare (popmax 0.000932%, nfe) (gnomAD).

What do computational predictors say about COL18A1 p.Gly485Val (c.1454G>T)?

AlphaMissense predicts likely benign (score 0.2898) — an in-silico prediction, not a clinical call.

COL18A1 p.Gly485Val

c.1454G>T · rs912817242 · VCV1438056

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2898 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000932%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2898	likely benign
REVEL	0.91	moderately pathogenic-leaning
SaProt	LLR -13.81	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 0.86, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 107 kb · p 4.9e-06 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM G900V vs ClinVar G485V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000932% European (non-Finnish) · 11/1,179,956 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000683% 11/1,610,728 alleles · very rare exomes 7/1,458,590 · genomes 4/152,138 · joint denominator

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.Gly485Val
Coding: c.1454G>T
MANE Select: NM_001379500
dbSNP: rs912817242
Type: single nucleotide variant
Location: chr21:45480701 (GRCh38)
Gene constraint: LOEUF 1.001 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 51.77 · 9 PDB
Residue 900 UniProt numbering: the 'triple-helical region 3 (col3)' region; the 'disordered' region

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

Similar variants

COL18A1 p.Gly485Cys Uncertain significance ★ ⚠ same residue
COL18A1 p.Gly485= Likely benign ★ same residue
COL18A1 c.1897-2A>G Likely pathogenic ★★ same type
COL18A1 c.2157+1G>A Likely pathogenic ★★ same type
COL18A1 c.2577+1G>A Pathogenic/Likely pathogenic ★★ same type
COL18A1 c.3013+3A>C Likely pathogenic ★★ same type
COL18A1 c.3809+2T>C Pathogenic ★★ same type
COL18A1 c.798+1G>T Likely 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-gly485val (accessed [today's date]).

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