Is DPP9 p.Asp48His (c.142G>C) pathogenic?

DPP9 p.Asp48His (c.142G>C) is classified Uncertain significance in DPP9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-17). AlphaMissense: likely benign (0.1009); Absent from gnomAD v4.1; Associated with hatipoglu immunodeficiency syndrome.

What condition is associated with DPP9 p.Asp48His (c.142G>C)?

DPP9 p.Asp48His (c.142G>C) is associated with hatipoglu immunodeficiency syndrome (ClinVar).

How common is DPP9 p.Asp48His (c.142G>C) in the general population?

DPP9 p.Asp48His (c.142G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DPP9 p.Asp48His (c.142G>C)?

AlphaMissense predicts likely benign (score 0.1009) — an in-silico prediction, not a clinical call.

DPP9 p.Asp48His

c.142G>C · VCV4056123

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1009 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hatipoglu immunodeficiency syndrome

Computational evidence

Protein change
AlphaMissense	0.1009	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -10.30	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP 0.31, phastCons 0.69
Regional constraint	o/e 0.88	unconstrained · MANE · 34 kb · p 0.00027 · regional, not allelic
Overall
CADD	21.8	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 D19H vs ClinVar D48H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DPP9
Protein: p.Asp48His
Coding: c.142G>C
MANE Select: NM_139159
Type: single nucleotide variant
Location: chr19:4714252 (GRCh38)
Gene constraint: LOEUF 0.647 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.96 · 14 PDB
Residue 48: an α-helix

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.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-asp48his (accessed [today's date]).

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