Is CTSF p.Lys260= (c.780G>A) pathogenic?

CTSF p.Lys260= (c.780G>A) is classified Likely benign in CTSF (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-11). Ultra-rare (popmax 0.0319%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CTSF p.Lys260= (c.780G>A)?

CTSF p.Lys260= (c.780G>A) is associated with Inborn genetic diseases, neuronal ceroid lipofuscinosis 13 (ClinVar).

How common is CTSF p.Lys260= (c.780G>A) in the general population?

CTSF p.Lys260= (c.780G>A) is ultra-rare (popmax 0.0319%, nfe) (gnomAD).

CTSF p.Lys260=

c.780G>A · rs140002533 · VCV720279

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0319%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.009	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.81	GERP -2.1, phastCons 0.25
Overall
CADD	5.575	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0319% European (non-Finnish) · 376/1,180,018 alleles

Filtering AF 0.0292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0281%

Overall 0.0243% 392/1,614,156 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0319%	3,138
Remaining individualsnot grpmax-eligible	0.016%	6,251
East Asian	0.00446%	22,440
Finnishnot grpmax-eligible	0.00312%	32,002
African / African-American	0.00266%	37,525

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.Lys260=
Coding: c.780G>A
MANE Select: NM_003793
dbSNP: rs140002533
Type: single nucleotide variant
Location: chr11:66566109 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: neuronal ceroid lipofuscinosis 13

Similar variants

CTSF c.1045+1G>T Likely pathogenic ★★ same condition
CTSF p.Arg217Ter Pathogenic ★★ same condition
CTSF p.Ala22Ser Uncertain significance ★★ ⚠ same condition
CTSF p.Arg121Pro Uncertain significance ★★ ⚠ same condition
CTSF p.Arg196Gln Uncertain significance ★★ ⚠ same condition
CTSF p.Arg196Trp Uncertain significance ★★ ⚠ same condition
CTSF p.Arg205Trp Uncertain significance ★★ ⚠ same condition
CTSF p.Arg413Cys 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-lys260 (accessed [today's date]).

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