Is CLN3 p.Val148del (c.443_445del) pathogenic?

CLN3 p.Val148del (c.443445del) is classified Uncertain significance in CLN3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-05-01). Very rare (popmax 0.00246%, nfe); Associated with neuronal ceroid lipofuscinosis.

What condition is associated with CLN3 p.Val148del (c.443_445del)?

CLN3 p.Val148del (c.443_445del) is associated with neuronal ceroid lipofuscinosis, intellectual disability (ClinVar).

How common is CLN3 p.Val148del (c.443_445del) in the general population?

CLN3 p.Val148del (c.443_445del) is very rare (popmax 0.00246%, nfe) (gnomAD).

CLN3 p.Val148del

c.443_445del · rs752130042 · VCV975365

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00246%, nfe)

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 -1.6	GERP -3.3
Overall
CADD	17.91	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00246% European (non-Finnish) · 29/1,179,816 alleles

Filtering AF 0.00172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.00186% 30/1,613,782 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00246%	40,683
Admixed American	0.00167%	59,956

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CLN3
Protein: p.Val148del
Coding: c.443_445del
MANE Select: NM_001042432
dbSNP: rs752130042
Type: Deletion
Location: chr16:28487471 (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

Also linked: intellectual disability

Similar variants

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.Gly187fs Pathogenic/Likely pathogenic ★★ same condition
CLN3 p.Leu214fs Pathogenic/Likely pathogenic ★★ same condition
CLN3 p.Leu359fs Pathogenic/Likely pathogenic ★★ same condition
CLN3 p.Leu46_Cys47insTer Pathogenic/Likely pathogenic ★★ same condition
CLN3 p.Phe331fs 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-val148del (accessed [today's date]).

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