Is CTSF p.Asp456= (c.1368C>T) pathogenic?

CTSF p.Asp456= (c.1368C>T) is classified Benign/Likely benign in CTSF (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-01-28). Low-frequency (popmax 2.52%, afr); Associated with Inborn genetic diseases.

What condition is associated with CTSF p.Asp456= (c.1368C>T)?

CTSF p.Asp456= (c.1368C>T) is associated with Inborn genetic diseases, neuronal ceroid lipofuscinosis 13 (ClinVar).

How common is CTSF p.Asp456= (c.1368C>T) in the general population?

CTSF p.Asp456= (c.1368C>T) is low-frequency (popmax 2.52%, afr) (gnomAD).

CTSF p.Asp456=

c.1368C>T · rs148155987 · VCV259167

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.52%, afr)

Conditions

Inborn genetic diseases

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 4.5	GERP 0.11, phastCons 1
Overall
CADD	8.328	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.52% African / African-American · 1,891/75,054 alleles

Filtering AF 2.42% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.39%

Overall 0.135% 2,172/1,613,684 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.52%	40
Remaining individualsnot grpmax-eligible	0.219%	456
Admixed American	0.18%	555
Middle Eastern	0.115%	866
South Asian	0.0121%	8,271
European (non-Finnish)	0.00153%	65,547

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.Asp456=
Coding: c.1368C>T
MANE Select: NM_003793
dbSNP: rs148155987
Type: single nucleotide variant
Location: chr11:66564100 (GRCh38)
Gene constraint: LOEUF 1.296 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.78 · 1 PDB
Residue 456: a disulfide bond

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-asp456 (accessed [today's date]).

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