Is CLN6 p.Pro70fs (c.209_214delinsACTGCGC) pathogenic?

CLN6 p.Pro70fs (c.209214delinsACTGCGC) is classified Likely pathogenic in CLN6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-09). Associated with ceroid lipofuscinosis, neuronal, 6A.

What condition is associated with CLN6 p.Pro70fs (c.209_214delinsACTGCGC)?

CLN6 p.Pro70fs (c.209_214delinsACTGCGC) is associated with ceroid lipofuscinosis, neuronal, 6A (ClinVar).

How is CLN6 disease inherited?

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

CLN6 p.Pro70fs

c.209_214delinsACTGCGC · VCV4815914

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

ceroid lipofuscinosis, neuronal, 6A

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 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.1	GERP -0.62, phastCons 1

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

Variant & gene context

Gene: CLN6
Protein: p.Pro70fs
Coding: c.209_214delinsACTGCGC
MANE Select: NM_017882
Type: Indel
Location: chr15:68214373 (GRCh38)
Gene constraint: LOEUF 1.015 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.86

Full CLN6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ceroid lipofuscinosis, neuronal, 6A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For CLN6 disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

CLN6 p.Phe238Thr Pathogenic/Likely pathogenic ★★ same condition
CLN6 p.Val277fs Pathogenic ★★ same condition
CLN6 c.486+1G>A Likely pathogenic ★★ same condition
CLN6 c.543-1G>A Likely pathogenic ★★ same condition
CLN6 c.665+1G>T Likely pathogenic ★★ same condition
CLN6 c.83+1G>C Likely pathogenic ★★ same condition
CLN6 c.84-1G>A Pathogenic/Likely pathogenic ★★ same condition
CLN6 p.Arg103Gln 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/cln6-p-pro70fs (accessed [today's date]).

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