Is CTSF p.Arg254= (c.762G>A) pathogenic?

CTSF p.Arg254= (c.762G>A) is classified Benign in CTSF (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-04). Common (popmax 83%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Inborn genetic diseases.

What condition is associated with CTSF p.Arg254= (c.762G>A)?

CTSF p.Arg254= (c.762G>A) is associated with Inborn genetic diseases, neuronal ceroid lipofuscinosis 13 (ClinVar).

CTSF p.Arg254=

Q: How common is CTSF p.Arg254= (c.762G>A) in the general population?

CTSF p.Arg254= (c.762G>A) is common (popmax 83%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.762G>A · rs545009 · VCV259172

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Common

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

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.062	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.17	GERP -4.8
Overall
CADD	1.572	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 83% African / African-American · 62,231/74,940 alleles

Filtering AF 82.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 82.3%

Overall 54.4% 877,318/1,613,860 alleles · common exomes 784,743/1,461,836 · genomes 92,575/152,024 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	83%	1
Finnishnot grpmax-eligible	63.2%	2
Remaining individualsnot grpmax-eligible	54.3%	2
European (non-Finnish)	54.2%	2
Ashkenazi Jewishnot grpmax-eligible	53.6%	2
Middle Eastern	51.8%	2
East Asian	51.4%	2
Amishnot grpmax-eligible	42.8%	2
South Asian	40.1%	2
Admixed American	36.8%	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.Arg254=
Coding: c.762G>A
MANE Select: NM_003793
dbSNP: rs545009
Type: single nucleotide variant
Location: chr11:66566127 (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-arg254 (accessed [today's date]).

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