Is CLN6 p.Arg250= (c.750C>T) pathogenic?

CLN6 p.Arg250= (c.750C>T) is classified Likely benign in CLN6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-13). Very rare (popmax 0.0022%, sas); Associated with neuronal ceroid lipofuscinosis.

What condition is associated with CLN6 p.Arg250= (c.750C>T)?

CLN6 p.Arg250= (c.750C>T) is associated with neuronal ceroid lipofuscinosis (ClinVar).

How common is CLN6 p.Arg250= (c.750C>T) in the general population?

CLN6 p.Arg250= (c.750C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

CLN6 p.Arg250=

c.750C>T · rs537994561 · VCV1364506

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

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
Pangolin	Δ0.44	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 0.31	GERP -3.9, phastCons 0.98
Overall
CADD	7.246	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,092 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000136%

Overall 0.000124% 2/1,614,120 alleles · very rare

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: CLN6
Protein: p.Arg250=
Coding: c.750C>T
MANE Select: NM_017882
dbSNP: rs537994561
Type: single nucleotide variant
Location: chr15:68208326 (GRCh38)
Gene constraint: LOEUF 1.015 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.86

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.Arg250His Uncertain significance ★★ ⚠ same residue
CLN6 p.Arg250Cys Uncertain significance ★ ⚠ same residue
CLN6 p.Arg250Gly 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-arg250 (accessed [today's date]).

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