Is DPP9 p.Arg828Cys (c.2482C>T) pathogenic?

DPP9 p.Arg828Cys (c.2482C>T) is classified Likely pathogenic in DPP9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: likely pathogenic (0.864); Absent from gnomAD v4.1; Associated with hatipoglu immunodeficiency syndrome.

What condition is associated with DPP9 p.Arg828Cys (c.2482C>T)?

DPP9 p.Arg828Cys (c.2482C>T) is associated with hatipoglu immunodeficiency syndrome (ClinVar).

How common is DPP9 p.Arg828Cys (c.2482C>T) in the general population?

DPP9 p.Arg828Cys (c.2482C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DPP9 p.Arg828Cys (c.2482C>T)?

AlphaMissense predicts likely pathogenic (score 0.864) — an in-silico prediction, not a clinical call.

DPP9 p.Arg828Cys

c.2482C>T · VCV4277662

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.864 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,611,562)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hatipoglu immunodeficiency syndrome

Computational evidence

Protein change
AlphaMissense	0.864	likely pathogenic ✓ concordant with ClinVar
REVEL	0.699	pathogenic-leaning
SaProt	LLR -13.35	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 1.4, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 8,223 bp · p 2e-05 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R799C vs ClinVar R828C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,611,562). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DPP9
Protein: p.Arg828Cys
Coding: c.2482C>T
MANE Select: NM_139159
Type: single nucleotide variant
Location: chr19:4679939 (GRCh38)
Gene constraint: LOEUF 0.647 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.96 · 14 PDB
Residue 828: a UniProt-annotated variant site (in hatis; likely pathogenic); a UniProt-annotated variant site (in hatis; likely pathogenic; no protein detected by wester blot analysis in homozygous patient cells)

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.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
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-arg828cys (accessed [today's date]).

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