Is COL2A1 p.Pro1213= (c.3639C>T) pathogenic?

COL2A1 p.Pro1213= (c.3639C>T) is classified Likely benign in COL2A1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-06). Ultra-rare (popmax 0.04%, afr).

How common is COL2A1 p.Pro1213= (c.3639C>T) in the general population?

COL2A1 p.Pro1213= (c.3639C>T) is ultra-rare (popmax 0.04%, afr) (gnomAD).

COL2A1 p.Pro1213=

c.3639C>T · rs375710692 · VCV1199888

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.04%, afr)

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 1.8	GERP -3.3, phastCons 1
Overall
CADD	9.124	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.04% African / African-American · 30/74,916 alleles

Filtering AF 0.0288% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0249%

Overall 0.00193% 31/1,602,476 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.04%	2,497
Remaining individualsnot grpmax-eligible	0.0016%	62,412

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.Pro1213=
Coding: c.3639C>T
MANE Select: NM_001844
dbSNP: rs375710692
Type: single nucleotide variant
Location: chr12:47975564 (GRCh38)
Gene constraint: LOEUF 0.183 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 53.56 · 11 PDB
Residue 1213: the 'disordered' region; a modified residue (3-hydroxyproline); the 'triple-helical region' region

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

Similar variants

COL2A1 p.Pro1213Thr Uncertain significance ★★ ⚠ same residue
COL2A1 p.Pro1213Ser Conflicting classifications of pathogenicity ★ ⚠ 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-pro1213 (accessed [today's date]).

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