Is CLN6 p.Phe263fs (c.786_787dup) pathogenic?

CLN6 p.Phe263fs (c.786787dup) is classified Likely pathogenic in CLN6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2018-02-16). Absent from gnomAD; Associated with ceroid lipofuscinosis, neuronal, 6A.

What condition is associated with CLN6 p.Phe263fs (c.786_787dup)?

CLN6 p.Phe263fs (c.786_787dup) is associated with ceroid lipofuscinosis, neuronal, 6A (ClinVar).

How common is CLN6 p.Phe263fs (c.786_787dup) in the general population?

CLN6 p.Phe263fs (c.786_787dup) is absent from gnomAD (gnomAD).

How is CLN6 disease inherited?

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

CLN6 p.Phe263fs

c.786_787dup · rs1555438229 · VCV556613

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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	escapes	premature termination codon in the last exon (7 of 7) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.1	GERP 2, 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: CLN6
Protein: p.Phe263fs
Coding: c.786_787dup
MANE Select: NM_017882
dbSNP: rs1555438229
Type: Microsatellite
Location: chr15:68208288 (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.Ser132fs Pathogenic ★★ same condition
CLN6 p.Phe263= Likely benign ★★ same residue
CLN6 p.Val32fs Likely pathogenic ★ same condition
CLN6 p.Ser265del Conflicting classifications of pathogenicity ★ same condition
CLN6 p.Ile119del Uncertain significance 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

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-phe263fs (accessed [today's date]).

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