TPP2 p.Ser260=

Q: Is TPP2 p.Ser260= (c.780T>C) pathogenic?

TPP2 p.Ser260= (c.780T>C) is classified Benign in TPP2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Common (popmax 60.2%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency.

Q: What condition is associated with TPP2 p.Ser260= (c.780T>C)?

TPP2 p.Ser260= (c.780T>C) is associated with Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency (ClinVar).

Q: How common is TPP2 p.Ser260= (c.780T>C) in the general population?

TPP2 p.Ser260= (c.780T>C) is common (popmax 60.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.780T>C · rs2230854 · VCV1170502

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 60.2%, afr) — too common for a highly-penetrant pathogenic allele

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 -0.3	GERP -4.4, phastCons 0.42
Overall
CADD	6.918	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 60.2% African / African-American · 44,911/74,664 alleles

Filtering AF 59.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 59.5%

Overall 47.4% 763,931/1,610,320 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	60.2%	2
Finnishnot grpmax-eligible	49.1%	2
East Asian	48.7%	2
European (non-Finnish)	48%	2
Remaining individualsnot grpmax-eligible	46.6%	2
Amishnot grpmax-eligible	45.2%	2
Middle Eastern	43.6%	2
Ashkenazi Jewishnot grpmax-eligible	40.9%	2
South Asian	38.1%	3
Admixed American	36.5%	3

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.Ser260=
Coding: c.780T>C
MANE Select: NM_001330588
dbSNP: rs2230854
Type: single nucleotide variant
Location: chr13:102623036 (GRCh38)
Gene constraint: LOEUF 0.29 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.98
Residue 260: 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-ser260 (accessed [today's date]).

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