Is CLN3 p.Ser186fs (c.555del) pathogenic?

CLN3 p.Ser186fs (c.555del) is classified Likely pathogenic in CLN3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-28). Absent from gnomAD; Associated with neuronal ceroid lipofuscinosis 3.

What condition is associated with CLN3 p.Ser186fs (c.555del)?

CLN3 p.Ser186fs (c.555del) is associated with neuronal ceroid lipofuscinosis 3 (ClinVar).

How common is CLN3 p.Ser186fs (c.555del) in the general population?

CLN3 p.Ser186fs (c.555del) is absent from gnomAD (gnomAD).

How is CLN3 disease inherited?

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

CLN3 p.Ser186fs

c.555del · rs2506483000 · VCV2680812

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

neuronal ceroid lipofuscinosis 3

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 9 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.7, 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: CLN3
Protein: p.Ser186fs
Coding: c.555del
MANE Select: NM_001042432
dbSNP: rs2506483000
Type: Deletion
Location: chr16:28486469 (GRCh38)
Gene constraint: LOEUF 1.022 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 81.81

Full CLN3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neuronal ceroid lipofuscinosis 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For CLN3 disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

CLN3 c.375-2del Likely pathogenic ★★ same condition
CLN3 c.461-280_677+382del Pathogenic ★★ same condition
CLN3 c.790+1del Pathogenic/Likely pathogenic ★★ same condition
CLN3 c.954_962+18del Pathogenic/Likely pathogenic ★★ same condition
CLN3 p.Glu244fs Pathogenic/Likely pathogenic ★★ same condition
CLN3 p.Glu273fs Pathogenic/Likely pathogenic ★★ same condition
CLN3 p.Gly187fs Pathogenic/Likely pathogenic ★★ same condition
CLN3 p.Leu214fs 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/cln3-p-ser186fs (accessed [today's date]).

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