Is CLN6 p.Pro75fs (c.224del) pathogenic?

CLN6 p.Pro75fs (c.224del) is classified Likely pathogenic in CLN6 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-10). Absent from gnomAD; Associated with congenital nervous system disorder.

What condition is associated with CLN6 p.Pro75fs (c.224del)?

CLN6 p.Pro75fs (c.224del) is associated with congenital nervous system disorder (ClinVar).

How common is CLN6 p.Pro75fs (c.224del) in the general population?

CLN6 p.Pro75fs (c.224del) is absent from gnomAD (gnomAD).

CLN6 p.Pro75fs

c.224del · rs2141141525 · VCV1180682

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

congenital nervous system disorder

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 3 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.4	GERP -3.2

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.Pro75fs
Coding: c.224del
MANE Select: NM_017882
dbSNP: rs2141141525
Type: Deletion
Location: chr15:68214363 (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

congenital nervous system disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CLN6 p.Pro75Leu Uncertain significance ★ ⚠ same residue
CLN6 p.Pro75= Likely benign ★ same residue
CLN6 c.83+1G>C Likely pathogenic ★★ same condition
CLN6 p.Val133fs Pathogenic/Likely pathogenic ★★ same condition
CLN6 p.Ile153fs Pathogenic/Likely pathogenic ★★ same type
CLN6 p.Phe120_Met122del Pathogenic/Likely pathogenic ★★ same type
CLN6 p.Phe60fs Pathogenic/Likely pathogenic ★★ same type
CLN6 p.Pro297fs Pathogenic/Likely pathogenic ★★ same type

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-pro75fs (accessed [today's date]).

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