Is CLN5 p.Gln140= (c.420A>G) pathogenic?

CLN5 p.Gln140= (c.420A>G) is classified Conflicting classifications of pathogenicity in CLN5 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-12-07). Ultra-rare (popmax 0.0657%, mid); Associated with neuronal ceroid lipofuscinosis.

What condition is associated with CLN5 p.Gln140= (c.420A>G)?

CLN5 p.Gln140= (c.420A>G) is associated with neuronal ceroid lipofuscinosis, neuronal ceroid lipofuscinosis 5 (ClinVar).

How common is CLN5 p.Gln140= (c.420A>G) in the general population?

CLN5 p.Gln140= (c.420A>G) is ultra-rare (popmax 0.0657%, mid) (gnomAD).

CLN5 p.Gln140=

c.420A>G · rs753732321 · VCV934097

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0657%, mid)

Conditions

neuronal ceroid lipofuscinosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.4	GERP -5.5
Overall
CADD	7.238	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0657% Middle Eastern · 4/6,084 alleles

Filtering AF 0.0224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.00198% 32/1,614,096 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0657%	1,521
African / African-American	0.00534%	18,734
Remaining individualsnot grpmax-eligible	0.0048%	20,829
European (non-Finnish)	0.00169%	59,002
South Asian	0.0011%	91,094

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: CLN5
Protein: p.Gln140=
Coding: c.420A>G
MANE Select: NM_006493
dbSNP: rs753732321
Type: single nucleotide variant
Location: chr13:76995982 (GRCh38)
Gene constraint: LOEUF 1.197 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.05 · 1 PDB
Residue 140: 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

Also linked: neuronal ceroid lipofuscinosis 5

Similar variants

CLN5 p.Gln140Ter Likely pathogenic 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
CLN5 p.Cys77Tyr 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-gln140 (accessed [today's date]).

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