Is TPP2 p.Val634= (c.1902T>C) pathogenic?

TPP2 p.Val634= (c.1902T>C) is classified Benign/Likely benign in TPP2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-03). Low-frequency (popmax 1.07%, afr); Associated with Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency.

How common is TPP2 p.Val634= (c.1902T>C) in the general population?

TPP2 p.Val634= (c.1902T>C) is low-frequency (popmax 1.07%, afr) (gnomAD).

TPP2 p.Val634=

Q: What condition is associated with TPP2 p.Val634= (c.1902T>C)?

TPP2 p.Val634= (c.1902T>C) is associated with Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency (ClinVar).

c.1902T>C · rs148056679 · VCV478052

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.07%, afr)

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 -1.5	GERP -5
Overall
CADD	2.381	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.07% African / African-American · 800/75,050 alleles

Filtering AF 1% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.98%

Overall 0.0576% 929/1,612,900 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.07%	94
Admixed American	0.112%	896
Remaining individualsnot grpmax-eligible	0.0752%	1,329
Middle Eastern	0.033%	3,031
South Asian	0.00439%	22,769
European (non-Finnish)	0.000763%	131,104

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.Val634=
Coding: c.1902T>C
MANE Select: NM_001330588
dbSNP: rs148056679
Type: single nucleotide variant
Location: chr13:102638304 (GRCh38)
Gene constraint: LOEUF 0.29 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.98

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-val634 (accessed [today's date]).

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