Is CLN8 p.Val236= (c.708C>T) pathogenic?

CLN8 p.Val236= (c.708C>T) is classified Likely benign in CLN8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-17). Ultra-rare (popmax 0.02%, afr); Associated with neuronal ceroid lipofuscinosis.

What condition is associated with CLN8 p.Val236= (c.708C>T)?

CLN8 p.Val236= (c.708C>T) is associated with neuronal ceroid lipofuscinosis (ClinVar).

How common is CLN8 p.Val236= (c.708C>T) in the general population?

CLN8 p.Val236= (c.708C>T) is ultra-rare (popmax 0.02%, afr) (gnomAD).

CLN8 p.Val236=

c.708C>T · rs200760828 · VCV377700

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, afr)

Conditions

neuronal ceroid lipofuscinosis

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 · C>A here scores Δ0.29 · evaluated, not missing
Constraint at this position
Conservation	phyloP -14	GERP -3.5
Overall
CADD	0.017	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% African / African-American · 15/75,060 alleles

Filtering AF 0.0123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00987%

Overall 0.00155% 25/1,614,218 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.02%	5,004
Middle Eastern	0.0165%	6,062
South Asian	0.00329%	30,363
Remaining individualsnot grpmax-eligible	0.0016%	62,506
European (non-Finnish)	0.000424%	236,008

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: CLN8
Protein: p.Val236=
Coding: c.708C>T
MANE Select: NM_018941
dbSNP: rs200760828
Type: single nucleotide variant
Location: chr8:1780414 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.47 · 3 PDB
Residue 236: the tlc domain

Full CLN8 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

CLN8 p.Val236Ile Uncertain significance ★ ⚠ same residue
CLN8 p.Val236Leu Uncertain significance ★ ⚠ same residue
CLN8 p.Val236fs Conflicting classifications of pathogenicity ★ same residue
CLN8 p.Arg204Cys Pathogenic/Likely pathogenic ★★ same condition
CLN8 p.Arg204His Likely pathogenic ★★ same condition
CLN8 p.Arg24Gly Pathogenic ★★ same condition
CLN8 p.Arg70Cys Pathogenic/Likely pathogenic ★★ same condition
CLN8 p.Arg70His 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/cln8-p-val236 (accessed [today's date]).

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