Is CLN5 p.Met1Val (c.1A>G) pathogenic?

CLN5 p.Met1Val (c.1A>G) is classified Uncertain significance in CLN5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2017-08-04). Absent from gnomAD v4.1; Associated with neuronal ceroid lipofuscinosis 5.

What condition is associated with CLN5 p.Met1Val (c.1A>G)?

CLN5 p.Met1Val (c.1A>G) is associated with neuronal ceroid lipofuscinosis 5 (ClinVar).

How common is CLN5 p.Met1Val (c.1A>G) in the general population?

CLN5 p.Met1Val (c.1A>G) is absent from gnomAD v4.1 (gnomAD).

CLN5 p.Met1Val

c.1A>G · rs1268502139 · VCV553182

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

start-loss

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

neuronal ceroid lipofuscinosis 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function
REVEL	0.052	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.2	GERP -3.5
Overall
CADD	4.923	PHRED · no single calibrated threshold — expert panels disagree

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

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.Met1Val
Coding: c.1A>G
MANE Select: NM_006493
dbSNP: rs1268502139
Type: single nucleotide variant
Location: chr13:76991952 (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.Met1Ile Uncertain significance ★★ same residue
CLN5 p.Met1Leu Uncertain significance ★★ 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
CLN5 p.Cys144Tyr 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-met1val (accessed [today's date]).

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