Is CCN6 p.Pro196fs (c.587del) pathogenic?

CCN6 p.Pro196fs (c.587del) is classified Pathogenic in CCN6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-12). Very rare (popmax 0.00102%, nfe).

How common is CCN6 p.Pro196fs (c.587del) in the general population?

CCN6 p.Pro196fs (c.587del) is very rare (popmax 0.00102%, nfe) (gnomAD).

CCN6 p.Pro196fs

c.587del · rs782293823 · VCV1680467

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

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 3 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.4	GERP 2.5, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00102% European (non-Finnish) · 12/1,179,902 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000821% 12/1,461,654 alleles · very rare

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.Pro196fs
Coding: c.587del
MANE Select: NM_198239
dbSNP: rs782293823
Type: Deletion
Location: chr6:112064994 (GRCh38)
Gene constraint: LOEUF 1.055 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.30
Residue 196: a UniProt-annotated variant site (in pprd)

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

Similar variants

CCN6 p.Asn178_Cys179insTer Pathogenic ★★ same type
CCN6 p.Glu84fs Pathogenic ★★ same type
CCN6 p.Ser236fs Pathogenic ★★ same type
CCN6 c.783+1_783+6del Pathogenic ★ same type
CCN6 p.Ala15fs Pathogenic ★ same type
CCN6 p.Glu32fs Pathogenic ★ same type
CCN6 p.Gly171fs Pathogenic ★ same type
CCN6 p.Leu210fs 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/ccn6-p-pro196fs (accessed [today's date]).

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