Is CLN3 p.Ser261= (c.783G>A) pathogenic?

CLN3 p.Ser261= (c.783G>A) is classified Likely benign in CLN3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-17). Very rare (popmax 0.00224%, eas); Associated with neuronal ceroid lipofuscinosis.

What condition is associated with CLN3 p.Ser261= (c.783G>A)?

CLN3 p.Ser261= (c.783G>A) is associated with neuronal ceroid lipofuscinosis (ClinVar).

How common is CLN3 p.Ser261= (c.783G>A) in the general population?

CLN3 p.Ser261= (c.783G>A) is very rare (popmax 0.00224%, eas) (gnomAD).

CLN3 p.Ser261=

c.783G>A · rs752632879 · VCV1535263

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Conditions

neuronal ceroid lipofuscinosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -6.7	GERP -2.6
Overall
CADD	12.99	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00224% East Asian · 1/44,732 alleles

Filtering AF 0.00043% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000684% 11/1,607,096 alleles · very rare exomes 10/1,454,936 · genomes 1/152,160 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00224%	44,732
European (non-Finnish)	0.00085%	117,682

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.Ser261=
Coding: c.783G>A
MANE Select: NM_001042432
dbSNP: rs752632879
Type: single nucleotide variant
Location: chr16:28484013 (GRCh38)
Gene constraint: LOEUF 1.022 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 81.81
Residue 261: the 'disordered' region

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.Ser261Leu 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-ser261 (accessed [today's date]).

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