Is CLN5 p.Phe192Val (c.574T>G) pathogenic?

CLN5 p.Phe192Val (c.574T>G) is classified Uncertain significance in CLN5 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-04-06). AlphaMissense: likely pathogenic (0.8514); Very rare (popmax 0.000678%, nfe); Associated with neuronal ceroid lipofuscinosis.

What condition is associated with CLN5 p.Phe192Val (c.574T>G)?

CLN5 p.Phe192Val (c.574T>G) is associated with neuronal ceroid lipofuscinosis (ClinVar).

How common is CLN5 p.Phe192Val (c.574T>G) in the general population?

CLN5 p.Phe192Val (c.574T>G) is very rare (popmax 0.000678%, nfe) (gnomAD).

What do computational predictors say about CLN5 p.Phe192Val (c.574T>G)?

AlphaMissense predicts likely pathogenic (score 0.8514) — an in-silico prediction, not a clinical call.

CLN5 p.Phe192Val

c.574T>G · rs1555274325 · VCV527741

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8514 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neuronal ceroid lipofuscinosis

Computational evidence

Protein change
AlphaMissense	0.8514	likely pathogenic
REVEL	0.798	moderately pathogenic-leaning
SaProt	LLR -9.89	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 8,867 bp · p 0.55 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000678% European (non-Finnish) · 8/1,179,626 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000548% 8/1,461,030 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.Phe192Val
Coding: c.574T>G
MANE Select: NM_006493
dbSNP: rs1555274325
Type: single nucleotide variant
Location: chr13:77000466 (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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CLN5 p.Phe192= 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
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-phe192val (accessed [today's date]).

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