Is DPP9 p.Leu181fs (c.541del) pathogenic?

DPP9 p.Leu181fs (c.541del) is classified Uncertain significance in DPP9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-28). Associated with hatipoglu immunodeficiency syndrome.

What condition is associated with DPP9 p.Leu181fs (c.541del)?

DPP9 p.Leu181fs (c.541del) is associated with hatipoglu immunodeficiency syndrome (ClinVar).

DPP9 p.Leu181fs

c.541del · VCV4078529

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

hatipoglu immunodeficiency syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1

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

Variant & gene context

Gene: DPP9
Protein: p.Leu181fs
Coding: c.541del
MANE Select: NM_139159
Type: Deletion
Location: chr19:4704190 (GRCh38)
Gene constraint: LOEUF 0.647 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.96 · 14 PDB
Residue 181: a UniProt-annotated variant site (in hatis; likely pathogenic)

Full DPP9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hatipoglu immunodeficiency syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DPP9 p.Asp310Asn Uncertain significance ★★ ⚠ same condition
DPP9 p.Thr301Met Uncertain significance ★★ ⚠ same condition
DPP9 p.Arg828Cys Likely pathogenic ★ same condition
DPP9 p.Arg645His Uncertain significance ★ ⚠ same condition
DPP9 p.Asp48His Uncertain significance ★ ⚠ same condition
DPP9 p.Asp84Asn Uncertain significance ★ ⚠ same condition
DPP9 p.Val489Ile Uncertain significance ★ ⚠ same condition
DPP9 p.Arg111Ter Pathogenic 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/dpp9-p-leu181fs (accessed [today's date]).

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