Is CLN3 p.Ser131= (c.393T>C) pathogenic?

CLN3 p.Ser131= (c.393T>C) is classified Conflicting classifications of pathogenicity in CLN3 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-07-19). Very rare (popmax 8.48e-05%, nfe); Associated with neuronal ceroid lipofuscinosis.

What condition is associated with CLN3 p.Ser131= (c.393T>C)?

CLN3 p.Ser131= (c.393T>C) is associated with neuronal ceroid lipofuscinosis (ClinVar).

How common is CLN3 p.Ser131= (c.393T>C) in the general population?

CLN3 p.Ser131= (c.393T>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

CLN3 p.Ser131=

c.393T>C · rs794727850 · VCV198450

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

neuronal ceroid lipofuscinosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.242	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.32	GERP -1.4, phastCons 0.6
Overall
CADD	4.73	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,790 alleles

Overall 6.84e-05% 1/1,461,634 alleles · very rare

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.Ser131=
Coding: c.393T>C
MANE Select: NM_001042432
dbSNP: rs794727850
Type: single nucleotide variant
Location: chr16:28487523 (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.Ser131Asn Uncertain significance ★★ ⚠ same residue
CLN3 p.Ser131Gly Uncertain significance ★ ⚠ same residue
CLN3 p.Ser131fs Pathogenic ★ 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

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-ser131 (accessed [today's date]).

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