Is CTSF p.Cys424Ter (c.1272C>A) pathogenic?

CTSF p.Cys424Ter (c.1272C>A) is classified Likely pathogenic in CTSF (ClinVar, Single submitter, 1 submitter; last evaluated 2020-09-04). Absent from gnomAD v4.1.

How common is CTSF p.Cys424Ter (c.1272C>A) in the general population?

CTSF p.Cys424Ter (c.1272C>A) is absent from gnomAD v4.1 (gnomAD).

CTSF p.Cys424Ter

c.1272C>A · rs2134949827 · VCV1690935

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,599,790)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 11 of 13
REVEL	0.057	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.21	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 2.9	GERP -1.5, phastCons 1
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,599,790). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CTSF
Protein: p.Cys424Ter
Coding: c.1272C>A
MANE Select: NM_003793
dbSNP: rs2134949827
Type: single nucleotide variant
Location: chr11:66564607 (GRCh38)
Gene constraint: LOEUF 1.296 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.78 · 1 PDB
Residue 424: a disulfide bond

Full CTSF gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CTSF c.1045+1G>T Likely pathogenic ★★ same type
CTSF p.Arg217Ter Pathogenic ★★ same type
CTSF p.Ala22Ser Uncertain significance ★★ ⚠ same type
CTSF p.Arg121Pro Uncertain significance ★★ ⚠ same type
CTSF p.Arg196Gln Uncertain significance ★★ ⚠ same type
CTSF p.Arg196Trp Uncertain significance ★★ same type
CTSF p.Arg205Trp Uncertain significance ★★ ⚠ same type
CTSF p.Arg413Cys Uncertain significance ★★ ⚠ same type

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-cys424ter (accessed [today's date]).

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