Is CLN5 p.Ser307= (c.921T>C) pathogenic?

CLN5 p.Ser307= (c.921T>C) is classified Likely benign in CLN5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-12). Very rare (popmax 0.00134%, afr); Associated with neuronal ceroid lipofuscinosis.

What condition is associated with CLN5 p.Ser307= (c.921T>C)?

CLN5 p.Ser307= (c.921T>C) is associated with neuronal ceroid lipofuscinosis (ClinVar).

How common is CLN5 p.Ser307= (c.921T>C) in the general population?

CLN5 p.Ser307= (c.921T>C) is very rare (popmax 0.00134%, afr) (gnomAD).

CLN5 p.Ser307=

c.921T>C · rs149668314 · VCV2034320

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

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 3.5	GERP 2.8, phastCons 1
Overall
CADD	8.796	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,668 alleles

Overall 6.86e-05% 1/1,457,770 alleles · very rare

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.Ser307=
Coding: c.921T>C
MANE Select: NM_006493
dbSNP: rs149668314
Type: single nucleotide variant
Location: chr13:77000813 (GRCh38)
Gene constraint: LOEUF 1.197 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.05 · 1 PDB
Residue 307: the 'membrane-anchoring' region

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.Ser307Asn Conflicting classifications of pathogenicity ★ ⚠ 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.Cys77Tyr Likely pathogenic ★★ ⚠ same condition
CLN5 p.Gln183Ter 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-ser307 (accessed [today's date]).

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