Is CTSF p.Arg121Pro (c.362G>C) pathogenic?

CTSF p.Arg121Pro (c.362G>C) is classified Uncertain significance in CTSF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-28). AlphaMissense: likely pathogenic (0.7764); Ultra-rare (popmax 0.0183%, amr); Associated with Inborn genetic diseases.

What condition is associated with CTSF p.Arg121Pro (c.362G>C)?

CTSF p.Arg121Pro (c.362G>C) is associated with Inborn genetic diseases (ClinVar).

How common is CTSF p.Arg121Pro (c.362G>C) in the general population?

CTSF p.Arg121Pro (c.362G>C) is ultra-rare (popmax 0.0183%, amr) (gnomAD).

What do computational predictors say about CTSF p.Arg121Pro (c.362G>C)?

AlphaMissense predicts likely pathogenic (score 0.7764) — an in-silico prediction, not a clinical call.

CTSF p.Arg121Pro

c.362G>C · rs369135126 · VCV590162

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7764 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0183%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7764	likely pathogenic
REVEL	0.255	benign-leaning
SaProt	LLR -10.22	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP 1.3, phastCons 0.99
Regional constraint	o/e 1.02	unconstrained · MANE · 4,550 bp · p 0.69 · regional, not allelic
Overall
CADD	20.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0183% Admixed American · 11/60,008 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00785%

Overall 0.00762% 123/1,614,092 alleles · ultra-rare exomes 108/1,461,868 · genomes 15/152,224 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0183%	5,455
African / African-American	0.00934%	10,706
European (non-Finnish)	0.00864%	11,569
Remaining individualsnot grpmax-eligible	0.0032%	31,243
South Asian	0.0011%	91,088

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.Arg121Pro
Coding: c.362G>C
MANE Select: NM_003793
dbSNP: rs369135126
Type: single nucleotide variant
Location: chr11:66567613 (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

Similar variants

CTSF c.1045+1G>T Likely pathogenic ★★ same condition
CTSF p.Arg217Ter Pathogenic ★★ same condition
CTSF p.Arg196Trp Uncertain significance ★★ same condition
CTSF p.Arg418Cys Uncertain significance ★★ ⚠ same condition
CTSF p.Arg421Gln Uncertain significance ★★ ⚠ same condition
CTSF p.Arg54Gly Uncertain significance ★★ ⚠ same condition
CTSF p.Asn213Lys Uncertain significance ★★ ⚠ same condition
CTSF p.Asn378Ser 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-arg121pro (accessed [today's date]).

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