Is CLN8 p.Asp17Val (c.50A>T) pathogenic?

CLN8 p.Asp17Val (c.50A>T) is classified Uncertain significance in CLN8 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-05). AlphaMissense: ambiguous (0.4206); Very rare (popmax 0.00133%, afr); Associated with neuronal ceroid lipofuscinosis.

What condition is associated with CLN8 p.Asp17Val (c.50A>T)?

CLN8 p.Asp17Val (c.50A>T) is associated with neuronal ceroid lipofuscinosis (ClinVar).

How common is CLN8 p.Asp17Val (c.50A>T) in the general population?

CLN8 p.Asp17Val (c.50A>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about CLN8 p.Asp17Val (c.50A>T)?

AlphaMissense predicts ambiguous (score 0.4206) — an in-silico prediction, not a clinical call.

CLN8 p.Asp17Val

c.50A>T · rs148668081 · VCV1395698

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4206 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

neuronal ceroid lipofuscinosis

Computational evidence

Protein change
AlphaMissense	0.4206	ambiguous
REVEL	0.855	moderately pathogenic-leaning
SaProt	LLR -10.83	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 9,509 bp · p 0.0075 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,944 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,613,862 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,944
European (non-Finnish)	0.000169%	589,995

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.Asp17Val
Coding: c.50A>T
MANE Select: NM_018941
dbSNP: rs148668081
Type: single nucleotide variant
Location: chr8:1771104 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.47 · 3 PDB

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.Asp17Gly Uncertain significance ★★ ⚠ 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
CLN8 p.Gln255Ter Pathogenic ★★ same condition
CLN8 p.Gln99Ter 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-asp17val (accessed [today's date]).

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