Is DPP9 p.Arg111Ter (c.331C>T) pathogenic?

DPP9 p.Arg111Ter (c.331C>T) is classified Pathogenic in DPP9 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-04-25). Very rare (popmax 0.000593%, nfe); Associated with hatipoglu immunodeficiency syndrome.

What condition is associated with DPP9 p.Arg111Ter (c.331C>T)?

DPP9 p.Arg111Ter (c.331C>T) is associated with hatipoglu immunodeficiency syndrome (ClinVar).

How common is DPP9 p.Arg111Ter (c.331C>T) in the general population?

DPP9 p.Arg111Ter (c.331C>T) is very rare (popmax 0.000593%, nfe) (gnomAD).

DPP9 p.Arg111Ter

c.331C>T · rs779854175 · VCV2500001

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Conditions

hatipoglu immunodeficiency syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 22
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP -3.6, phastCons 1
Overall
CADD	42.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000593% European (non-Finnish) · 7/1,179,696 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000558% 9/1,613,572 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,448
Finnishnot grpmax-eligible	0.00156%	63,988
European (non-Finnish)grpmax	0.000593%	168,528

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DPP9
Protein: p.Arg111Ter
Coding: c.331C>T
MANE Select: NM_139159
dbSNP: rs779854175
Type: single nucleotide variant
Location: chr19:4705953 (GRCh38)
Gene constraint: LOEUF 0.647 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.96 · 14 PDB
Residue 111: a UniProt-annotated variant site (in hatis; likely pathogenic); a β-strand

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.Gln851Ter 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-arg111ter (accessed [today's date]).

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