Is COL18A1 p.Pro986= (c.2958T>C) pathogenic?

COL18A1 p.Pro986= (c.2958T>C) is classified Likely benign in COL18A1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-11). Ultra-rare (popmax 0.0609%, afr).

How common is COL18A1 p.Pro986= (c.2958T>C) in the general population?

COL18A1 p.Pro986= (c.2958T>C) is ultra-rare (popmax 0.0609%, afr) (gnomAD).

COL18A1 p.Pro986=

c.2958T>C · rs1040197101 · VCV1119719

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0609%, afr)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.61	GERP -2.4, phastCons 0.046
Overall
CADD	1.751	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0609% African / African-American · 42/68,988 alleles

Filtering AF 0.0462% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0411%

Overall 0.00652% 103/1,580,792 alleles · ultra-rare exomes 83/1,432,354 · genomes 20/148,438 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0609%	1,643
Middle Eastern	0.0507%	1,973
South Asian	0.0303%	3,295
Ashkenazi Jewishnot grpmax-eligible	0.00686%	14,582
Remaining individualsnot grpmax-eligible	0.00654%	15,288
European (non-Finnish)	0.00215%	46,473

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.Pro986=
Coding: c.2958T>C
MANE Select: NM_001379500
dbSNP: rs1040197101
Type: single nucleotide variant
Location: chr21:45505223 (GRCh38)

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

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-pro986 (accessed [today's date]).

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