Is CCN6 p.Trp216fs (c.646_647dup) pathogenic?

CCN6 p.Trp216fs (c.646647dup) is classified Pathogenic in CCN6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-07). Absent from gnomAD.

How common is CCN6 p.Trp216fs (c.646_647dup) in the general population?

CCN6 p.Trp216fs (c.646_647dup) is absent from gnomAD (gnomAD).

CCN6 p.Trp216fs

c.646_647dup · rs2546928953 · VCV2044417

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 4 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3	GERP 0.12, phastCons 1

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.Trp216fs
Coding: c.646_647dup
MANE Select: NM_198239
dbSNP: rs2546928953
Type: Duplication
Location: chr6:112068260 (GRCh38)
Gene constraint: LOEUF 1.055 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.30
Residue 216: a UniProt-annotated variant site (in pprd); the tsp type-1 domain

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

Similar variants

CCN6 p.Trp216Cys Uncertain significance ★ ⚠ same residue
CCN6 p.Cys209fs Pathogenic ★★ same type
CCN6 p.Gln289fs Pathogenic/Likely pathogenic ★★ same type
CCN6 c.48+2dup Pathogenic ★ same type
CCN6 p.Glu243fs Pathogenic ★ same type
CCN6 p.Leu160fs Pathogenic ★ same type
CCN6 p.Ser228fs Pathogenic ★ same type
CCN6 p.Ser290fs 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-trp216fs (accessed [today's date]).

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