Is CLN5 p.Ile83Ser (c.248T>G) pathogenic?

CLN5 p.Ile83Ser (c.248T>G) is classified Uncertain significance in CLN5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-31). AlphaMissense: likely pathogenic (0.6817); Absent from gnomAD v4.1; Associated with neuronal ceroid lipofuscinosis.

What condition is associated with CLN5 p.Ile83Ser (c.248T>G)?

CLN5 p.Ile83Ser (c.248T>G) is associated with neuronal ceroid lipofuscinosis (ClinVar).

How common is CLN5 p.Ile83Ser (c.248T>G) in the general population?

CLN5 p.Ile83Ser (c.248T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLN5 p.Ile83Ser (c.248T>G)?

AlphaMissense predicts likely pathogenic (score 0.6817) — an in-silico prediction, not a clinical call.

CLN5 p.Ile83Ser

c.248T>G · rs2034243356 · VCV1357888

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6817 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

neuronal ceroid lipofuscinosis

Computational evidence

Protein change
AlphaMissense	0.6817	likely pathogenic
REVEL	0.629	indeterminate
SaProt	LLR -11.36	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP 1.6, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 8,867 bp · p 0.55 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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: CLN5
Protein: p.Ile83Ser
Coding: c.248T>G
MANE Select: NM_006493
dbSNP: rs2034243356
Type: single nucleotide variant
Location: chr13:76995137 (GRCh38)
Gene constraint: LOEUF 1.197 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.05 · 1 PDB
Residue 83: a disulfide bond

Full CLN5 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

CLN5 p.Ile83Thr Uncertain significance ★ ⚠ same residue
CLN5 p.Ile83Val Uncertain significance ★ ⚠ same residue
CLN5 p.Ile83= Likely benign ★ same residue
CLN5 c.174-2A>G Likely pathogenic ★★ same condition
CLN5 p.Arg150Ter Pathogenic ★★ same condition
CLN5 p.Arg63His Pathogenic/Likely pathogenic ★★ ⚠ same condition
CLN5 p.Arg96Ter Pathogenic/Likely pathogenic ★★ same condition
CLN5 p.Asn143Ser 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/cln5-p-ile83ser (accessed [today's date]).

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