Is COL2A1 p.Pro1142= (c.3426C>T) pathogenic?

COL2A1 p.Pro1142= (c.3426C>T) is classified Likely benign in COL2A1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-06-01). Ultra-rare (popmax 0.0329%, mid).

How common is COL2A1 p.Pro1142= (c.3426C>T) in the general population?

COL2A1 p.Pro1142= (c.3426C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

COL2A1 p.Pro1142=

c.3426C>T · rs755031857 · VCV1151875

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

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 -5.7	GERP -3.8
Overall
CADD	0.614	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,072 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.009%

Overall 0.00316% 51/1,612,732 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,036
Admixed American	0.02%	4,991
Remaining individualsnot grpmax-eligible	0.00801%	12,488
African / African-American	0.00534%	18,724
South Asian	0.0044%	22,708
European (non-Finnish)	0.00203%	49,148

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.Pro1142=
Coding: c.3426C>T
MANE Select: NM_001844
dbSNP: rs755031857
Type: single nucleotide variant
Location: chr12:47976821 (GRCh38)
Gene constraint: LOEUF 0.183 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 53.56 · 11 PDB
Residue 1142: an α-helix; 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.Pro1142His Uncertain significance ★ ⚠ same residue
COL2A1 p.Pro1142Ser Uncertain significance ★ ⚠ 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-pro1142 (accessed [today's date]).

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