Is CLN6 p.Trp56Ter (c.168G>A) pathogenic?

CLN6 p.Trp56Ter (c.168G>A) is classified Pathogenic/Likely pathogenic in CLN6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-15). Very rare (popmax 6.84e-05%); Associated with ceroid lipofuscinosis, neuronal, 6A.

What condition is associated with CLN6 p.Trp56Ter (c.168G>A)?

CLN6 p.Trp56Ter (c.168G>A) is associated with ceroid lipofuscinosis, neuronal, 6A, neuronal ceroid lipofuscinosis (ClinVar).

How common is CLN6 p.Trp56Ter (c.168G>A) in the general population?

CLN6 p.Trp56Ter (c.168G>A) is very rare (popmax 6.84e-05%) (gnomAD).

How is CLN6 disease inherited?

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

CLN6 p.Trp56Ter

c.168G>A · rs1477757203 · VCV2911779

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Conditions

ceroid lipofuscinosis, neuronal, 6A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 7
REVEL	0.568	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.5, phastCons 1
Overall
CADD	42.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.84e-05%

Overall 6.84e-05% 1/1,461,674 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.Trp56Ter
Coding: c.168G>A
MANE Select: NM_017882
dbSNP: rs1477757203
Type: single nucleotide variant
Location: chr15:68218566 (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

Also linked: neuronal ceroid lipofuscinosis

For CLN6 disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

CLN6 c.297+1G>A Pathogenic/Likely 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>A Pathogenic/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-trp56ter (accessed [today's date]).

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