Is TPP2 p.Ser801= (c.2403T>C) pathogenic?

TPP2 p.Ser801= (c.2403T>C) is classified Likely benign in TPP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-31). Very rare (popmax 0.0011%, sas); Associated with Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency.

How common is TPP2 p.Ser801= (c.2403T>C) in the general population?

TPP2 p.Ser801= (c.2403T>C) is very rare (popmax 0.0011%, sas) (gnomAD).

TPP2 p.Ser801=

Q: What condition is associated with TPP2 p.Ser801= (c.2403T>C)?

TPP2 p.Ser801= (c.2403T>C) is associated with Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency (ClinVar).

c.2403T>C · rs752264020 · VCV2185757

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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	<0.2	all four deltas below 0.2 · T>G here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.4	GERP 2.5, phastCons 1
Overall
CADD	12.59	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/90,818 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000205% 3/1,460,132 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	90,818
European (non-Finnish)	0.00017%	589,668

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: TPP2
Protein: p.Ser801=
Coding: c.2403T>C
MANE Select: NM_001330588
dbSNP: rs752264020
Type: single nucleotide variant
Location: chr13:102646303 (GRCh38)
Gene constraint: LOEUF 0.29 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.98
Residue 801: 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.Ser801Asn Uncertain significance ★★ ⚠ same residue
TPP2 p.Ser801Arg Uncertain significance ★ ⚠ same residue
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

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-ser801 (accessed [today's date]).

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