Is CLN3 p.Ser69= (c.207G>A) pathogenic?

CLN3 p.Ser69= (c.207G>A) is classified Likely benign in CLN3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-07). Ultra-rare (popmax 0.0134%, eas); Associated with neuronal ceroid lipofuscinosis.

What condition is associated with CLN3 p.Ser69= (c.207G>A)?

CLN3 p.Ser69= (c.207G>A) is associated with neuronal ceroid lipofuscinosis (ClinVar).

How common is CLN3 p.Ser69= (c.207G>A) in the general population?

CLN3 p.Ser69= (c.207G>A) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

CLN3 p.Ser69=

c.207G>A · rs551476103 · VCV386233

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

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 -0.026	GERP -3.3, phastCons 0.004
Overall
CADD	1.312	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% East Asian · 6/44,848 alleles

Filtering AF 0.00679% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00524%

Overall 0.00161% 26/1,612,804 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,475
South Asian	0.0121%	8,251
Remaining individualsnot grpmax-eligible	0.0016%	62,450
European (non-Finnish)	0.000678%	147,434

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.Ser69=
Coding: c.207G>A
MANE Select: NM_001042432
dbSNP: rs551476103
Type: single nucleotide variant
Location: chr16:28489305 (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.Ser69Leu Uncertain significance ★★ ⚠ same residue
CLN3 p.Ser69Trp Uncertain significance ★★ ⚠ same residue
CLN3 p.Ser69Ter 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-ser69 (accessed [today's date]).

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