Is CLN6 p.Leu253= (c.759C>T) pathogenic?

CLN6 p.Leu253= (c.759C>T) is classified Likely benign in CLN6 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-02-18). Absent from gnomAD v4.1; Associated with neuronal ceroid lipofuscinosis.

What condition is associated with CLN6 p.Leu253= (c.759C>T)?

CLN6 p.Leu253= (c.759C>T) is associated with neuronal ceroid lipofuscinosis (ClinVar).

How common is CLN6 p.Leu253= (c.759C>T) in the general population?

CLN6 p.Leu253= (c.759C>T) is absent from gnomAD v4.1 (gnomAD).

CLN6 p.Leu253=

c.759C>T · rs1567094628 · VCV1534887

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP -0.23, phastCons 1
Overall
CADD	7.733	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CLN6
Protein: p.Leu253=
Coding: c.759C>T
MANE Select: NM_017882
dbSNP: rs1567094628
Type: single nucleotide variant
Location: chr15:68208317 (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.Leu253Val Uncertain significance ★★ ⚠ same residue
CLN6 p.Leu253Phe Uncertain significance ★ ⚠ same residue
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.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-leu253 (accessed [today's date]).

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