Is COL2A1 p.Arg1281= (c.3843C>T) pathogenic?

COL2A1 p.Arg1281= (c.3843C>T) is classified Benign/Likely benign in COL2A1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-20). Ultra-rare (popmax 0.0254%, afr).

How common is COL2A1 p.Arg1281= (c.3843C>T) in the general population?

COL2A1 p.Arg1281= (c.3843C>T) is ultra-rare (popmax 0.0254%, afr) (gnomAD).

COL2A1 p.Arg1281=

c.3843C>T · rs752970787 · VCV1001920

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0254%, 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 0.76	GERP -1.6, phastCons 1
Overall
CADD	7.192	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0254% African / African-American · 19/74,930 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0137%

Overall 0.00124% 20/1,614,068 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0254%	3,944
Admixed American	0.00167%	60,016

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.Arg1281=
Coding: c.3843C>T
MANE Select: NM_001844
dbSNP: rs752970787
Type: single nucleotide variant
Location: chr12:47975360 (GRCh38)
Gene constraint: LOEUF 0.183 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 53.56 · 11 PDB
Residue 1281: the fibrillar collagen nc1 domain

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

Similar variants

COL2A1 p.Arg1281Cys Uncertain significance ★★ ⚠ same residue
COL2A1 p.Arg1281His 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-arg1281 (accessed [today's date]).

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