Is CLN3 p.Arg334= (c.1002C>T) pathogenic?

CLN3 p.Arg334= (c.1002C>T) is classified Likely benign in CLN3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-24). Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with CLN3 p.Arg334= (c.1002C>T)?

CLN3 p.Arg334= (c.1002C>T) is associated with Inborn genetic diseases, neuronal ceroid lipofuscinosis (ClinVar).

How common is CLN3 p.Arg334= (c.1002C>T) in the general population?

CLN3 p.Arg334= (c.1002C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

CLN3 p.Arg334=

c.1002C>T · rs140828382 · VCV590047

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Inborn genetic diseases

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 0.16	GERP -3, phastCons 0.89
Overall
CADD	7.877	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,938 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000806% 13/1,613,712 alleles · very rare exomes 7/1,461,608 · genomes 6/152,104 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,938
African / African-American	0.00134%	74,900
European (non-Finnish)	0.000932%	107,269

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.Arg334=
Coding: c.1002C>T
MANE Select: NM_001042432
dbSNP: rs140828382
Type: single nucleotide variant
Location: chr16:28482159 (GRCh38)
Gene constraint: LOEUF 1.022 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 81.81
Residue 334: a UniProt-annotated variant site (in cln3; does not affect lysosomal localization. does not affect lysosomal protein catabolic process. does not affect lysosomal ph); a UniProt-annotated variant site (in cln3)

Full CLN3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: neuronal ceroid lipofuscinosis

Similar variants

CLN3 p.Arg334Cys Pathogenic/Likely pathogenic ★★ same residue
CLN3 p.Arg334His Pathogenic/Likely 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
CLN3 c.125+1G>C 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-arg334 (accessed [today's date]).

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