Is CLN5 p.Arg63= (c.189T>C) pathogenic?

CLN5 p.Arg63= (c.189T>C) is classified Likely benign in CLN5 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-07). Absent from gnomAD v4.1; Associated with neuronal ceroid lipofuscinosis.

What condition is associated with CLN5 p.Arg63= (c.189T>C)?

CLN5 p.Arg63= (c.189T>C) is associated with neuronal ceroid lipofuscinosis (ClinVar).

How common is CLN5 p.Arg63= (c.189T>C) in the general population?

CLN5 p.Arg63= (c.189T>C) is absent from gnomAD v4.1 (gnomAD).

CLN5 p.Arg63=

c.189T>C · rs2154034624 · VCV1093487

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 -0.02	GERP -2.1, phastCons 0.91
Overall
CADD	6.976	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: CLN5
Protein: p.Arg63=
Coding: c.189T>C
MANE Select: NM_006493
dbSNP: rs2154034624
Type: single nucleotide variant
Location: chr13:76995078 (GRCh38)
Gene constraint: LOEUF 1.197 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.05 · 1 PDB
Residue 63: a UniProt-annotated variant site (in cln5; retained in the endoplasmic reticulum rather than reaching the lysosome)

Full CLN5 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

CLN5 p.Arg63His Pathogenic/Likely pathogenic ★★ ⚠ same residue
CLN5 p.Arg63Leu Uncertain significance ★★ ⚠ same residue
CLN5 p.Arg63Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
CLN5 p.Arg63Pro Conflicting classifications of pathogenicity ★ ⚠ same residue
CLN5 p.Arg63fs Pathogenic/Likely pathogenic ★★ same residue
CLN5 c.174-2A>G Likely pathogenic ★★ same condition
CLN5 p.Arg150Ter Pathogenic ★★ same condition
CLN5 p.Arg96Ter 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/cln5-p-arg63 (accessed [today's date]).

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