Is CTSF p.Gly73= (c.219T>C) pathogenic?

CTSF p.Gly73= (c.219T>C) is classified Benign in CTSF (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-04). Common (popmax 83%, afr) — too common for a highly-penetrant pathogenic allele; Associated with neuronal ceroid lipofuscinosis 13.

What condition is associated with CTSF p.Gly73= (c.219T>C)?

CTSF p.Gly73= (c.219T>C) is associated with neuronal ceroid lipofuscinosis 13 (ClinVar).

CTSF p.Gly73=

Q: How common is CTSF p.Gly73= (c.219T>C) in the general population?

CTSF p.Gly73= (c.219T>C) is common (popmax 83%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.219T>C · rs1127894 · VCV259169

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Common

common (popmax 83%, afr) — too common for a highly-penetrant pathogenic allele

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 2	GERP -4.8, phastCons 0.79
Overall
CADD	8.362	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 83% African / African-American · 60,462/72,844 alleles

Filtering AF 82.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 82.2%

Overall 54% 850,457/1,575,052 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	83%	1
Finnishnot grpmax-eligible	62%	2
European (non-Finnish)	54%	2
Remaining individualsnot grpmax-eligible	53.8%	2
Ashkenazi Jewishnot grpmax-eligible	53.1%	2
East Asian	49.9%	2
Middle Eastern	48.2%	2
Amishnot grpmax-eligible	42.8%	2
South Asian	39%	3
Admixed American	34.8%	3

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.Gly73=
Coding: c.219T>C
MANE Select: NM_003793
dbSNP: rs1127894
Type: single nucleotide variant
Location: chr11:66568077 (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 p.Gly73Ser Uncertain significance ★ ⚠ same residue
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

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-gly73 (accessed [today's date]).

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