Is CTSF p.Asp443= (c.1329C>T) pathogenic?

CTSF p.Asp443= (c.1329C>T) is classified Likely benign in CTSF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-14). Rare (popmax 0.276%, eas); Associated with neuronal ceroid lipofuscinosis 13.

What condition is associated with CTSF p.Asp443= (c.1329C>T)?

CTSF p.Asp443= (c.1329C>T) is associated with neuronal ceroid lipofuscinosis 13 (ClinVar).

How common is CTSF p.Asp443= (c.1329C>T) in the general population?

CTSF p.Asp443= (c.1329C>T) is rare (popmax 0.276%, eas) (gnomAD).

CTSF p.Asp443=

c.1329C>T · rs746980424 · VCV739506

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.276%, eas)

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 -0.75	GERP -4.2
Overall
CADD	5.551	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.276% East Asian · 124/44,860 alleles

Filtering AF 0.237% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.222%

Overall 0.00943% 152/1,611,574 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.276%	362
Middle Eastern	0.0329%	3,041
Remaining individualsnot grpmax-eligible	0.00481%	20,799
South Asian	0.00221%	45,257
European (non-Finnish)	0.00178%	56,144

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.Asp443=
Coding: c.1329C>T
MANE Select: NM_003793
dbSNP: rs746980424
Type: single nucleotide variant
Location: chr11:66564139 (GRCh38)
Gene constraint: LOEUF 1.296 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.78 · 1 PDB
Residue 443: a disulfide bond

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-asp443 (accessed [today's date]).

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