Is CTSF p.Leu62= (c.186G>A) pathogenic?

CTSF p.Leu62= (c.186G>A) is classified Likely benign in CTSF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-22). Ultra-rare (popmax 0.0272%, mid); Associated with neuronal ceroid lipofuscinosis 13.

What condition is associated with CTSF p.Leu62= (c.186G>A)?

CTSF p.Leu62= (c.186G>A) is associated with neuronal ceroid lipofuscinosis 13 (ClinVar).

How common is CTSF p.Leu62= (c.186G>A) in the general population?

CTSF p.Leu62= (c.186G>A) is ultra-rare (popmax 0.0272%, mid) (gnomAD).

CTSF p.Leu62=

c.186G>A · VCV3682006

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0272%, mid)

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 1.3	GERP -0.85, phastCons 0.67
Overall
CADD	10.73	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0272% Middle Eastern · 1/3,672 alleles

Filtering AF 0.00342% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00218%

Overall 0.000742% 9/1,213,742 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0272%	3,672
South Asian	0.00886%	11,288
European (non-Finnish)	0.00028%	357,094

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: CTSF
Protein: p.Leu62=
Coding: c.186G>A
MANE Select: NM_003793
Type: single nucleotide variant
Location: chr11:66568301 (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 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
CTSF p.Leu428Pro 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-leu62 (accessed [today's date]).

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