Is CCN6 p.Phe280fs (c.840del) pathogenic?

CCN6 p.Phe280fs (c.840del) is classified Pathogenic in CCN6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2004-07-01). Absent from gnomAD; Associated with progressive pseudorheumatoid arthropathy of childhood.

What condition is associated with CCN6 p.Phe280fs (c.840del)?

CCN6 p.Phe280fs (c.840del) is associated with progressive pseudorheumatoid arthropathy of childhood (ClinVar).

How common is CCN6 p.Phe280fs (c.840del) in the general population?

CCN6 p.Phe280fs (c.840del) is absent from gnomAD (gnomAD).

How is Progressive pseudorheumatoid dysplasia inherited?

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

CCN6 p.Phe280fs

c.840del · rs797044440 · VCV6389

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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	escapes	premature termination codon in the last exon (5 of 5) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1	GERP -4.8, phastCons 0.99

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CCN6
Protein: p.Phe280fs
Coding: c.840del
MANE Select: NM_198239
dbSNP: rs797044440
Type: Deletion
Location: chr6:112069393 (GRCh38)
Gene constraint: LOEUF 1.055 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.30
Residue 280: a disulfide bond; a UniProt-annotated variant site (in pprd); the ctck domain

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.Glu84fs Pathogenic ★★ same condition
CCN6 p.Ser236fs Pathogenic ★★ same condition
CCN6 p.Ala15fs Pathogenic ★ same condition
CCN6 p.Leu246fs Pathogenic ★ same condition
CCN6 p.Pro26fs Likely pathogenic ★ same condition
CCN6 p.Tyr198_Asn200delinsTer Pathogenic ★ same condition
CCN6 p.Val231fs Pathogenic same condition
CCN6 c.49-1G>A Pathogenic/Likely 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-phe280fs (accessed [today's date]).

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