Is CTSF p.Ala82= (c.246C>A) pathogenic?

CTSF p.Ala82= (c.246C>A) is classified Likely benign in CTSF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-25). Very rare (popmax 0.00528%, amr); Associated with Inborn genetic diseases.

What condition is associated with CTSF p.Ala82= (c.246C>A)?

CTSF p.Ala82= (c.246C>A) is associated with Inborn genetic diseases, neuronal ceroid lipofuscinosis 13 (ClinVar).

How common is CTSF p.Ala82= (c.246C>A) in the general population?

CTSF p.Ala82= (c.246C>A) is very rare (popmax 0.00528%, amr) (gnomAD).

CTSF p.Ala82=

c.246C>A · rs756262196 · VCV588106

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00528%, amr)

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 -0.05	GERP -4.8, phastCons 0.65
Overall
CADD	6.928	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00528% Admixed American · 3/56,776 alleles

Filtering AF 0.0014% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000689%

Overall 0.000345% 5/1,450,586 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00528%	18,925
Remaining individualsnot grpmax-eligible	0.00161%	61,944
European (non-Finnish)	8.5e-05%	1,175,939

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.Ala82=
Coding: c.246C>A
MANE Select: NM_003793
dbSNP: rs756262196
Type: single nucleotide variant
Location: chr11:66568050 (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 p.Ala82_Glu85del Uncertain significance ★ same residue
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

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-ala82 (accessed [today's date]).

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