Is CLN6 p.Phe239= (c.717C>T) pathogenic?

CLN6 p.Phe239= (c.717C>T) is classified Likely benign in CLN6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-02). Very rare (popmax 0.005%, amr); Associated with ceroid lipofuscinosis, neuronal, 6A.

What condition is associated with CLN6 p.Phe239= (c.717C>T)?

CLN6 p.Phe239= (c.717C>T) is associated with ceroid lipofuscinosis, neuronal, 6A, ceroid lipofuscinosis, neuronal, 6B (Kufs type), neuronal ceroid lipofuscinosis (ClinVar).

How common is CLN6 p.Phe239= (c.717C>T) in the general population?

CLN6 p.Phe239= (c.717C>T) is very rare (popmax 0.005%, amr) (gnomAD).

How is CLN6 disease inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CLN6 p.Phe239=

c.717C>T · rs745850620 · VCV699191

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

ceroid lipofuscinosis, neuronal, 6A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.59 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.1	GERP -4.1
Overall
CADD	8.889	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,010 alleles

Filtering AF 0.00153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.00211% 34/1,613,784 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,003
Remaining individualsnot grpmax-eligible	0.0048%	20,827
European (non-Finnish)	0.0022%	45,386
African / African-American	0.00133%	74,934
South Asian	0.0011%	91,092

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.Phe239=
Coding: c.717C>T
MANE Select: NM_017882
dbSNP: rs745850620
Type: single nucleotide variant
Location: chr15:68208359 (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

ceroid lipofuscinosis, neuronal, 6A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ceroid lipofuscinosis, neuronal, 6B (Kufs type)neuronal ceroid lipofuscinosis

For CLN6 disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

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.665+1G>T Likely pathogenic ★★ same condition
CLN6 c.83+1G>C 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-phe239 (accessed [today's date]).

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