Is CLN3 p.Leu129Pro (c.386_387delinsCT) pathogenic?

CLN3 p.Leu129Pro (c.386387delinsCT) is classified Uncertain significance in CLN3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-15). Absent from gnomAD; Associated with neuronal ceroid lipofuscinosis.

What condition is associated with CLN3 p.Leu129Pro (c.386_387delinsCT)?

CLN3 p.Leu129Pro (c.386_387delinsCT) is associated with neuronal ceroid lipofuscinosis (ClinVar).

How common is CLN3 p.Leu129Pro (c.386_387delinsCT) in the general population?

CLN3 p.Leu129Pro (c.386_387delinsCT) is absent from gnomAD (gnomAD).

CLN3 p.Leu129Pro

c.386_387delinsCT · rs2506492698 · VCV2112341

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

neuronal ceroid lipofuscinosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.7	GERP -3.3
Regional constraint	o/e 0.93	unconstrained · MANE · 14 kb · p 0.08 · regional, not allelic

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.Leu129Pro
Coding: c.386_387delinsCT
MANE Select: NM_001042432
dbSNP: rs2506492698
Type: Indel
Location: chr16:28487529 (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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CLN3 p.Leu129= Likely benign ★★ same residue
CLN3 c.1056+1G>A Likely pathogenic ★★ same condition
CLN3 c.1056+1G>T Likely pathogenic ★★ same condition
CLN3 c.1056+3A>C Pathogenic/Likely pathogenic ★★ same condition
CLN3 c.1197+1G>A Pathogenic/Likely pathogenic ★★ same condition
CLN3 c.1198-1G>T Pathogenic/Likely pathogenic ★★ same condition
CLN3 c.125+1G>C Pathogenic ★★ same condition
CLN3 c.222+1G>A 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-leu129pro (accessed [today's date]).

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