Is CLN6 p.Phe266= (c.798C>T) pathogenic?

CLN6 p.Phe266= (c.798C>T) is classified Conflicting classifications of pathogenicity in CLN6 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-07). Ultra-rare (popmax 0.0226%, afr); Associated with neuronal ceroid lipofuscinosis.

What condition is associated with CLN6 p.Phe266= (c.798C>T)?

CLN6 p.Phe266= (c.798C>T) is associated with neuronal ceroid lipofuscinosis (ClinVar).

How common is CLN6 p.Phe266= (c.798C>T) in the general population?

CLN6 p.Phe266= (c.798C>T) is ultra-rare (popmax 0.0226%, afr) (gnomAD).

CLN6 p.Phe266=

c.798C>T · rs140319056 · VCV595294

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0226%, afr)

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 -3.9	GERP -4.1
Overall
CADD	2.798	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0226% African / African-American · 17/75,056 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0118%

Overall 0.00198% 32/1,614,174 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0226%	4,415
Admixed American	0.005%	20,009
Remaining individualsnot grpmax-eligible	0.0016%	62,506
European (non-Finnish)	0.000932%	107,277

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.Phe266=
Coding: c.798C>T
MANE Select: NM_017882
dbSNP: rs140319056
Type: single nucleotide variant
Location: chr15:68208278 (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.Phe266Ser 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
CLN6 p.Arg103Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
CLN6 p.Arg149Cys 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-phe266 (accessed [today's date]).

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