Is CLN8 p.Ala30Pro (c.88G>C) pathogenic?

CLN8 p.Ala30Pro (c.88G>C) is classified Pathogenic in CLN8 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2006-05-01). AlphaMissense: likely pathogenic (0.6463); Absent from gnomAD v4.1; Associated with neuronal ceroid lipofuscinosis 8.

What condition is associated with CLN8 p.Ala30Pro (c.88G>C)?

CLN8 p.Ala30Pro (c.88G>C) is associated with neuronal ceroid lipofuscinosis 8 (ClinVar).

How common is CLN8 p.Ala30Pro (c.88G>C) in the general population?

CLN8 p.Ala30Pro (c.88G>C) is absent from gnomAD v4.1 (gnomAD).

How is CLN8 disease inherited?

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

What do computational predictors say about CLN8 p.Ala30Pro (c.88G>C)?

AlphaMissense predicts likely pathogenic (score 0.6463) — an in-silico prediction, not a clinical call.

CLN8 p.Ala30Pro

c.88G>C · rs137852883 · VCV2806

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6463 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neuronal ceroid lipofuscinosis 8

Computational evidence

Protein change
AlphaMissense	0.6463	likely pathogenic ✓ concordant with ClinVar
REVEL	0.702	pathogenic-leaning
SaProt	LLR -10.78	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 2, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 9,509 bp · p 0.0075 · regional, not allelic
Overall
CADD	19.23	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CLN8
Protein: p.Ala30Pro
Coding: c.88G>C
MANE Select: NM_018941
dbSNP: rs137852883
Type: single nucleotide variant
Location: chr8:1771142 (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 30: a UniProt-annotated variant site (in cln8)

Full CLN8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neuronal ceroid lipofuscinosis 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For CLN8 disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

CLN8 p.Ala30Ser Uncertain significance ★ ⚠ same residue
CLN8 p.Ala30fs Pathogenic/Likely pathogenic same residue
CLN8 p.Ala30Thr Uncertain significance ★★ ⚠ same residue
CLN8 p.Ala30= Likely benign ★ 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

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-ala30pro (accessed [today's date]).

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