Is TPP2 p.Pro948fs (c.2843del) pathogenic?

TPP2 p.Pro948fs (c.2843del) is classified Pathogenic in TPP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-08-15). Absent from gnomAD; Associated with Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency.

How common is TPP2 p.Pro948fs (c.2843del) in the general population?

TPP2 p.Pro948fs (c.2843del) is absent from gnomAD (gnomAD).

TPP2 p.Pro948fs

Q: What condition is associated with TPP2 p.Pro948fs (c.2843del)?

TPP2 p.Pro948fs (c.2843del) is associated with Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency (ClinVar).

c.2843del · rs1595188566 · VCV663284

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 22 of 30
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.5	GERP -0.49, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: TPP2
Protein: p.Pro948fs
Coding: c.2843del
MANE Select: NM_001330588
dbSNP: rs1595188566
Type: Deletion
Location: chr13:102649120 (GRCh38)
Gene constraint: LOEUF 0.29 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.98
Residue 948: a UniProt-annotated variant site (in imd78; loss of expression)

Full TPP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TPP2 p.Gly1156fs Pathogenic ★ same condition
TPP2 p.Tyr356fs Pathogenic ★ same condition
TPP2 c.1245-179_1245-6del Uncertain significance ★ same condition
TPP2 c.939+9_939+12del Uncertain significance ★ same condition
TPP2 c.1144+16del Benign ★ same condition
TPP2 c.1244+8del Likely benign ★ same condition
TPP2 c.1837-16del Likely benign ★ same condition
TPP2 c.1837-20_1837-17del Likely benign ★ 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/tpp2-p-pro948fs (accessed [today's date]).

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