Is COL2A1 p.Pro893= (c.2679G>A) pathogenic?

COL2A1 p.Pro893= (c.2679G>A) is classified Uncertain significance in COL2A1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-31). Very rare (popmax 0.00243%, eas).

How common is COL2A1 p.Pro893= (c.2679G>A) in the general population?

COL2A1 p.Pro893= (c.2679G>A) is very rare (popmax 0.00243%, eas) (gnomAD).

COL2A1 p.Pro893=

c.2679G>A · rs369684691 · VCV1427480

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00243%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.26 · evaluated, not missing
Pangolin	Δ0.23	loss · gain 0.04 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP -0.062	GERP -0.41, phastCons 0.53
Overall
CADD	22.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00243% East Asian · 1/41,136 alleles

Filtering AF 0.00125% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00107%

Overall 0.00219% 34/1,553,978 alleles · very rare exomes 32/1,401,932 · genomes 2/152,046 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0135%	7,426
East Asiangrpmax	0.00243%	41,136
South Asian	0.00238%	42,102
European (non-Finnish)	0.00192%	52,213
Remaining individualsnot grpmax-eligible	0.00166%	60,190

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: COL2A1
Protein: p.Pro893=
Coding: c.2679G>A
MANE Select: NM_001844
dbSNP: rs369684691
Type: single nucleotide variant
Location: chr12:47980009 (GRCh38)
Gene constraint: LOEUF 0.183 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 53.56 · 11 PDB
Residue 893: the 'disordered' region; the 'triple-helical region' region

Full COL2A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COL2A1 p.Pro893Leu Uncertain significance ★★ ⚠ same residue
COL2A1 p.Pro893fs Pathogenic ★★ same residue
COL2A1 c.1023+1G>A Pathogenic ★★ same type
COL2A1 c.1024-2A>C Pathogenic ★★ same type
COL2A1 c.1069-2A>G Pathogenic/Likely pathogenic ★★ same type
COL2A1 c.1221+1G>A Pathogenic ★★ same type
COL2A1 c.1222-2A>G Pathogenic ★★ same type
COL2A1 c.1365+1G>A Pathogenic/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/col2a1-p-pro893 (accessed [today's date]).

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