Is CCN6 p.Gln269= (c.807A>G) pathogenic?

CCN6 p.Gln269= (c.807A>G) is classified Benign in CCN6 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-04). Common (popmax 7.6%, mid) — too common for a highly-penetrant pathogenic allele; Associated with progressive pseudorheumatoid arthropathy of childhood.

What condition is associated with CCN6 p.Gln269= (c.807A>G)?

CCN6 p.Gln269= (c.807A>G) 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.Gln269=

Q: How common is CCN6 p.Gln269= (c.807A>G) in the general population?

CCN6 p.Gln269= (c.807A>G) is common (popmax 7.6%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.807A>G · rs17219737 · VCV355065

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 7.6%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

progressive pseudorheumatoid arthropathy of childhood

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 3.5	GERP -2.8, phastCons 1
Overall
CADD	6.011	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.6% Middle Eastern · 460/6,054 alleles

Filtering AF 7.03% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.8%

Overall 5.61% 90,546/1,613,014 alleles · common

Ancestry group	Frequency	1 in
Middle Easterngrpmax	7.6%	13
Amishnot grpmax-eligible	6.69%	15
European (non-Finnish)	6.58%	15
Ashkenazi Jewishnot grpmax-eligible	6.23%	16
Remaining individualsnot grpmax-eligible	5.52%	18
Admixed American	3.93%	25
Finnishnot grpmax-eligible	3.67%	27
South Asian	1.65%	60
African / African-American	1.28%	78
East Asian	0.0112%	8,964

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: CCN6
Protein: p.Gln269=
Coding: c.807A>G
MANE Select: NM_198239
dbSNP: rs17219737
Type: single nucleotide variant
Location: chr6:112069362 (GRCh38)
Gene constraint: LOEUF 1.055 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.30
Residue 269: 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 c.49-1G>A Pathogenic/Likely pathogenic ★★ same condition
CCN6 c.590-1G>C Likely pathogenic ★★ same condition
CCN6 p.Ala197Pro Pathogenic/Likely pathogenic ★★ ⚠ same condition
CCN6 p.Cys223Gly Pathogenic ★★ same condition
CCN6 p.Cys337Tyr Pathogenic/Likely pathogenic ★★ same condition
CCN6 p.Cys52Ter Pathogenic/Likely pathogenic ★★ same condition
CCN6 p.Cys78Tyr Pathogenic/Likely pathogenic ★★ same condition
CCN6 p.Met1Val 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-gln269 (accessed [today's date]).

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