Is CLN6 p.Arg149= (c.447T>C) pathogenic?

CLN6 p.Arg149= (c.447T>C) is classified Likely benign in CLN6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-30). Absent from gnomAD v4.1; Associated with neuronal ceroid lipofuscinosis.

What condition is associated with CLN6 p.Arg149= (c.447T>C)?

CLN6 p.Arg149= (c.447T>C) is associated with neuronal ceroid lipofuscinosis (ClinVar).

How common is CLN6 p.Arg149= (c.447T>C) in the general population?

CLN6 p.Arg149= (c.447T>C) is absent from gnomAD v4.1 (gnomAD).

CLN6 p.Arg149=

c.447T>C · VCV4698531

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 -11	GERP -2.7
Overall
CADD	0.294	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: CLN6
Protein: p.Arg149=
Coding: c.447T>C
MANE Select: NM_017882
Type: single nucleotide variant
Location: chr15:68211714 (GRCh38)
Gene constraint: LOEUF 1.015 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.86
Residue 149: a UniProt-annotated variant site (in cln6); a UniProt-annotated variant site (in cln4a)

Full CLN6 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

CLN6 p.Arg149Cys Likely pathogenic ★★ same residue
CLN6 p.Arg149His Uncertain significance ★★ ⚠ same residue
CLN6 p.Arg149Pro Uncertain significance ★ ⚠ same residue
CLN6 c.297+1G>A Pathogenic/Likely pathogenic ★★ same condition
CLN6 c.486+1G>A Likely pathogenic ★★ same condition
CLN6 c.543-1G>A Likely pathogenic ★★ same condition
CLN6 c.665+1G>A Pathogenic/Likely pathogenic ★★ same condition
CLN6 c.84-1G>A 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/cln6-p-arg149 (accessed [today's date]).

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