Is CCN6 p.Pro62fs (c.185del) pathogenic?

CCN6 p.Pro62fs (c.185del) is classified Pathogenic in CCN6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-28). Very rare (popmax 0.000678%, nfe).

How common is CCN6 p.Pro62fs (c.185del) in the general population?

CCN6 p.Pro62fs (c.185del) is very rare (popmax 0.000678%, nfe) (gnomAD).

CCN6 p.Pro62fs

c.185del · rs2546919941 · VCV2734927

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000678%, 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 2 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000678% European (non-Finnish) · 8/1,180,034 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000616% 9/1,461,882 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,508
European (non-Finnish)grpmax	0.000678%	147,504

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro62fs
Coding: c.185del
MANE Select: NM_198239
dbSNP: rs2546919941
Type: Deletion
Location: chr6:112061125 (GRCh38)
Gene constraint: LOEUF 1.055 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.30
Residue 62: a disulfide bond; a UniProt-annotated variant site (in pprd); the igfbp n-terminal domain

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-pro62fs (accessed [today's date]).

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