Is TPP2 p.Ile355= (c.1065T>C) pathogenic?

TPP2 p.Ile355= (c.1065T>C) is classified Likely benign in TPP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-04-01). Absent from gnomAD v4.1; Associated with Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency.

How common is TPP2 p.Ile355= (c.1065T>C) in the general population?

TPP2 p.Ile355= (c.1065T>C) is absent from gnomAD v4.1 (gnomAD).

TPP2 p.Ile355=

Q: What condition is associated with TPP2 p.Ile355= (c.1065T>C)?

TPP2 p.Ile355= (c.1065T>C) is associated with Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency (ClinVar).

c.1065T>C · rs2139484711 · VCV1123000

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,535,226)

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.014	GERP -2.5, phastCons 0.95
Overall
CADD	10.01	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,535,226). 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.Ile355=
Coding: c.1065T>C
MANE Select: NM_001330588
dbSNP: rs2139484711
Type: single nucleotide variant
Location: chr13:102629530 (GRCh38)
Gene constraint: LOEUF 0.29 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.98
Residue 355: the peptidase s8 domain

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.Ala619Thr Uncertain significance ★★ ⚠ same condition
TPP2 p.Ala648Asp Uncertain significance ★★ ⚠ same condition
TPP2 p.Arg1072Gln Uncertain significance ★★ ⚠ same condition
TPP2 p.Arg893Cys Uncertain significance ★★ ⚠ same condition
TPP2 p.Asn1192Ser Uncertain significance ★★ ⚠ same condition
TPP2 p.Asn1227Ser Uncertain significance ★★ ⚠ same condition
TPP2 p.Asp86His Uncertain significance ★★ ⚠ same condition
TPP2 p.Cys1231Tyr 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/tpp2-p-ile355 (accessed [today's date]).

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