Is CTSF p.Pro42= (c.126C>T) pathogenic?

CTSF p.Pro42= (c.126C>T) is classified Benign in CTSF (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). Common (popmax 27.5%, mid) — too common for a highly-penetrant pathogenic allele; Associated with neuronal ceroid lipofuscinosis 13.

What condition is associated with CTSF p.Pro42= (c.126C>T)?

CTSF p.Pro42= (c.126C>T) is associated with neuronal ceroid lipofuscinosis 13 (ClinVar).

CTSF p.Pro42=

Q: How common is CTSF p.Pro42= (c.126C>T) in the general population?

CTSF p.Pro42= (c.126C>T) is common (popmax 27.5%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.126C>T · rs1044522 · VCV259166

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 27.5%, mid) — 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 0.086	GERP -3.4, phastCons 0.11
Overall
CADD	9.989	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 27.5% Middle Eastern · 949/3,452 alleles

Filtering AF 26% ClinGen BA1/BS1 input FAF95, joint · FAF99 25.5%

Overall 23.6% 307,592/1,303,162 alleles · common

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	28.9%	3
Middle Easterngrpmax	27.5%	4
European (non-Finnish)	24.2%	4
Remaining individualsnot grpmax-eligible	23.8%	4
East Asian	23.6%	4
African / African-American	23.2%	4
Finnishnot grpmax-eligible	20.3%	5
Admixed American	18.8%	5
Amishnot grpmax-eligible	16.8%	6
South Asian	12.4%	8

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro42=
Coding: c.126C>T
MANE Select: NM_003793
dbSNP: rs1044522
Type: single nucleotide variant
Location: chr11:66568361 (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 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-pro42 (accessed [today's date]).

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