Is CLN5 p.Val214fs (c.639_640insTT) pathogenic?

CLN5 p.Val214fs (c.639640insTT) is classified Pathogenic in CLN5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-17). Absent from gnomAD; Associated with neuronal ceroid lipofuscinosis 5.

What condition is associated with CLN5 p.Val214fs (c.639_640insTT)?

CLN5 p.Val214fs (c.639_640insTT) is associated with neuronal ceroid lipofuscinosis 5 (ClinVar).

How common is CLN5 p.Val214fs (c.639_640insTT) in the general population?

CLN5 p.Val214fs (c.639_640insTT) is absent from gnomAD (gnomAD).

CLN5 p.Val214fs

c.639_640insTT · rs2501155081 · VCV2435733

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

neuronal ceroid lipofuscinosis 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (4 of 4) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.1	GERP 2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CLN5
Protein: p.Val214fs
Coding: c.639_640insTT
MANE Select: NM_006493
dbSNP: rs2501155081
Type: Insertion
Location: chr13:77000530 (GRCh38)
Gene constraint: LOEUF 1.197 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.05 · 1 PDB

Full CLN5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neuronal ceroid lipofuscinosis 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For CLN5 disease (Orphanet):

Onset: Infancy

Similar variants

CLN5 p.Val214= Conflicting classifications of pathogenicity ★ same residue
CLN5 p.Ile207fs Likely pathogenic ★ same condition
CLN5 p.Gly128fs Likely pathogenic same condition
CLN5 c.174-2A>G Likely pathogenic ★★ same condition
CLN5 c.340-52_365delinsTAACGGG Likely pathogenic ★★ same condition
CLN5 p.Arg150Ter Pathogenic ★★ same condition
CLN5 p.Arg258fs Pathogenic/Likely pathogenic ★★ same condition
CLN5 p.Arg63fs 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-val214fs (accessed [today's date]).

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