Is CLN6 p.Phe60= (c.180T>C) pathogenic?

CLN6 p.Phe60= (c.180T>C) is classified Likely benign in CLN6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-23). Ultra-rare (popmax 0.0164%, mid); Associated with neuronal ceroid lipofuscinosis.

What condition is associated with CLN6 p.Phe60= (c.180T>C)?

CLN6 p.Phe60= (c.180T>C) is associated with neuronal ceroid lipofuscinosis (ClinVar).

How common is CLN6 p.Phe60= (c.180T>C) in the general population?

CLN6 p.Phe60= (c.180T>C) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

CLN6 p.Phe60=

c.180T>C · rs1183583039 · VCV514196

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

neuronal ceroid lipofuscinosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.209	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.6	GERP -3
Overall
CADD	2.503	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.00062% 10/1,613,640 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
Admixed American	0.00167%	59,990
Remaining individualsnot grpmax-eligible	0.0016%	62,462
European (non-Finnish)	0.000593%	168,535

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.Phe60=
Coding: c.180T>C
MANE Select: NM_017882
dbSNP: rs1183583039
Type: single nucleotide variant
Location: chr15:68218554 (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.Phe60Ser Uncertain significance ★ ⚠ same residue
CLN6 p.Phe60fs Pathogenic/Likely pathogenic ★★ 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

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-phe60 (accessed [today's date]).

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