Is CLN3 p.Ser14= (c.42C>A) pathogenic?

CLN3 p.Ser14= (c.42C>A) is classified Likely benign in CLN3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-15). Absent from gnomAD v4.1; Associated with neuronal ceroid lipofuscinosis.

What condition is associated with CLN3 p.Ser14= (c.42C>A)?

CLN3 p.Ser14= (c.42C>A) is associated with neuronal ceroid lipofuscinosis (ClinVar).

How common is CLN3 p.Ser14= (c.42C>A) in the general population?

CLN3 p.Ser14= (c.42C>A) is absent from gnomAD v4.1 (gnomAD).

CLN3 p.Ser14=

c.42C>A · rs751155598 · VCV3008302

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 -1.9	GERP -3
Overall
CADD	6.582	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: CLN3
Protein: p.Ser14=
Coding: c.42C>A
MANE Select: NM_001042432
dbSNP: rs751155598
Type: single nucleotide variant
Location: chr16:28491718 (GRCh38)
Gene constraint: LOEUF 1.022 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 81.81
Residue 14: the 'disordered' region; a modified residue (phosphoserine)

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.Ser14Phe Uncertain significance ★ ⚠ 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-ser14 (accessed [today's date]).

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