Is CCN6 p.Pro26fs (c.76_83del) pathogenic?

CCN6 p.Pro26fs (c.7683del) is classified Likely pathogenic in CCN6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-27). Associated with progressive pseudorheumatoid arthropathy of childhood.

What condition is associated with CCN6 p.Pro26fs (c.76_83del)?

CCN6 p.Pro26fs (c.76_83del) is associated with progressive pseudorheumatoid arthropathy of childhood (ClinVar).

How is Progressive pseudorheumatoid dysplasia inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CCN6 p.Pro26fs

c.76_83del · VCV3392543

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

progressive pseudorheumatoid arthropathy of childhood

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.4	GERP 0.7, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: CCN6
Protein: p.Pro26fs
Coding: c.76_83del
MANE Select: NM_198239
Type: Deletion
Location: chr6:112061016 (GRCh38)
Gene constraint: LOEUF 1.055 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.30

Full CCN6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

progressive pseudorheumatoid arthropathy of childhood — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Progressive pseudorheumatoid dysplasia (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

CCN6 p.Pro26= Benign ★★ same residue
CCN6 p.Pro26Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
CCN6 p.Glu84fs Pathogenic ★★ same condition
CCN6 p.Ser236fs Pathogenic ★★ same condition
CCN6 p.Pro26Ala Uncertain significance ★★ ⚠ same residue
CCN6 p.Ala15fs Pathogenic ★ same condition
CCN6 p.Leu246fs Pathogenic ★ same condition
CCN6 p.Tyr198_Asn200delinsTer Pathogenic ★ same condition

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/ccn6-p-pro26fs (accessed [today's date]).

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