Is CTSF p.Arg54= (c.160C>A) pathogenic?

CTSF p.Arg54= (c.160C>A) is classified Conflicting classifications of pathogenicity in CTSF (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-28). Ultra-rare (popmax 0.0294%, amr); Associated with neuronal ceroid lipofuscinosis 13.

What condition is associated with CTSF p.Arg54= (c.160C>A)?

CTSF p.Arg54= (c.160C>A) is associated with neuronal ceroid lipofuscinosis 13 (ClinVar).

How common is CTSF p.Arg54= (c.160C>A) in the general population?

CTSF p.Arg54= (c.160C>A) is ultra-rare (popmax 0.0294%, amr) (gnomAD).

CTSF p.Arg54=

c.160C>A · rs776443007 · VCV1382735

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 0.0294%, amr)

Conditions

neuronal ceroid lipofuscinosis 13

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 10	GERP 2.2, phastCons 1
Overall
CADD	15.06	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0294% Admixed American · 7/23,844 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00968%

Overall 0.00859% 113/1,315,514 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.349%	286
Remaining individualsnot grpmax-eligible	0.0423%	2,366
Admixed Americangrpmax	0.0294%	3,406
European (non-Finnish)	0.00182%	54,876

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CTSF
Protein: p.Arg54=
Coding: c.160C>A
MANE Select: NM_003793
dbSNP: rs776443007
Type: single nucleotide variant
Location: chr11:66568327 (GRCh38)
Gene constraint: LOEUF 1.296 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.78 · 1 PDB

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

Disease context

neuronal ceroid lipofuscinosis 13 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For CLN13 disease (Orphanet):

Onset: Adolescent, Adult, Childhood, Elderly

Similar variants

CTSF p.Arg54Gly Uncertain significance ★★ ⚠ same residue
CTSF c.1045+1G>T Likely pathogenic ★★ same condition
CTSF p.Ala22Ser Uncertain significance ★★ ⚠ same condition
CTSF p.Arg196Gln Uncertain significance ★★ ⚠ same condition
CTSF p.Arg205Trp Uncertain significance ★★ ⚠ same condition
CTSF p.Arg413Cys Uncertain significance ★★ ⚠ same condition
CTSF p.Gly415Arg Uncertain significance ★★ ⚠ same condition
CTSF p.Gly439Ser Uncertain significance ★★ ⚠ 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/ctsf-p-arg54 (accessed [today's date]).

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