Is CTSF p.Tyr438= (c.1314C>T) pathogenic?

CTSF p.Tyr438= (c.1314C>T) is classified Likely benign in CTSF (ClinVar, Single submitter, 2 submitters; last evaluated 2026-01-25). Ultra-rare (popmax 0.0922%, afr); Associated with neuronal ceroid lipofuscinosis 13.

What condition is associated with CTSF p.Tyr438= (c.1314C>T)?

CTSF p.Tyr438= (c.1314C>T) is associated with neuronal ceroid lipofuscinosis 13 (ClinVar).

How common is CTSF p.Tyr438= (c.1314C>T) in the general population?

CTSF p.Tyr438= (c.1314C>T) is ultra-rare (popmax 0.0922%, afr) (gnomAD).

CTSF p.Tyr438=

c.1314C>T · rs149687246 · VCV2713142

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0922%, afr)

Conditions

neuronal ceroid lipofuscinosis 13

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.40 · evaluated, not missing
Constraint at this position
Conservation	phyloP -6.7	GERP -3.5
Overall
CADD	0.573	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0922% African / African-American · 68/73,746 alleles

Filtering AF 0.0746% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0682%

Overall 0.00596% 93/1,561,414 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0922%	1,084
South Asian	0.00705%	14,181
Admixed American	0.00577%	17,337
Remaining individualsnot grpmax-eligible	0.00496%	20,162
East Asian	0.00239%	41,896
European (non-Finnish)	0.00104%	96,111

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.Tyr438=
Coding: c.1314C>T
MANE Select: NM_003793
dbSNP: rs149687246
Type: single nucleotide variant
Location: chr11:66564565 (GRCh38)
Gene constraint: LOEUF 1.296 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.78 · 1 PDB
Residue 438: a disulfide bond; a β-strand

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-tyr438 (accessed [today's date]).

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