Is CLN6 p.Tyr142fs (c.424dup) pathogenic?

CLN6 p.Tyr142fs (c.424dup) is classified Pathogenic in CLN6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-03). Very rare (popmax 8.47e-05%, nfe); Associated with neuronal ceroid lipofuscinosis.

What condition is associated with CLN6 p.Tyr142fs (c.424dup)?

CLN6 p.Tyr142fs (c.424dup) is associated with neuronal ceroid lipofuscinosis (ClinVar).

How common is CLN6 p.Tyr142fs (c.424dup) in the general population?

CLN6 p.Tyr142fs (c.424dup) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

CLN6 p.Tyr142fs

c.424dup · rs1215499352 · VCV2915493

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

neuronal ceroid lipofuscinosis

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 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 1.4, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,012 alleles

Overall 6.84e-05% 1/1,461,752 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: CLN6
Protein: p.Tyr142fs
Coding: c.424dup
MANE Select: NM_017882
dbSNP: rs1215499352
Type: Duplication
Location: chr15:68211736 (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

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

Similar variants

CLN6 p.Tyr142Ter Pathogenic ★ same residue
CLN6 p.Tyr142= Likely benign ★ same residue
CLN6 p.Arg106fs Pathogenic ★★ same condition
CLN6 p.Glu167Ter Pathogenic/Likely pathogenic ★★ same condition
CLN6 p.Val133fs Pathogenic/Likely pathogenic ★★ same condition
CLN6 p.Val91fs Pathogenic ★★ same condition
CLN6 c.83+14dup Benign/Likely benign ★★ same condition
CLN6 p.Asp83fs 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-tyr142fs (accessed [today's date]).

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