Is CTSF p.Arg59= (c.177G>A) pathogenic?

CTSF p.Arg59= (c.177G>A) is classified Likely benign in CTSF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-16). Rare (popmax 0.111%, sas); Associated with Inborn genetic diseases.

What condition is associated with CTSF p.Arg59= (c.177G>A)?

CTSF p.Arg59= (c.177G>A) is associated with Inborn genetic diseases, neuronal ceroid lipofuscinosis 13 (ClinVar).

How common is CTSF p.Arg59= (c.177G>A) in the general population?

CTSF p.Arg59= (c.177G>A) is rare (popmax 0.111%, sas) (gnomAD).

CTSF p.Arg59=

c.177G>A · rs533565350 · VCV1779955

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.111%, sas)

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 0.51	GERP 1.4, phastCons 0.092
Overall
CADD	10.61	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.111% South Asian · 53/47,826 alleles

Filtering AF 0.087% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0784%

Overall 0.00449% 60/1,335,026 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.111%	902
Admixed American	0.0124%	8,054
Remaining individualsnot grpmax-eligible	0.00198%	50,540
European (non-Finnish)	0.000285%	351,363

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.Arg59=
Coding: c.177G>A
MANE Select: NM_003793
dbSNP: rs533565350
Type: single nucleotide variant
Location: chr11:66568310 (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-arg59 (accessed [today's date]).

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