Is DPP9 p.Gly167Ser (c.499G>A) pathogenic?

DPP9 p.Gly167Ser (c.499G>A) is classified Conflicting classifications of pathogenicity in DPP9 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2024-02-03). AlphaMissense: likely pathogenic (0.9735); Very rare (popmax 8.48e-05%, nfe); Associated with hatipoglu immunodeficiency syndrome.

What condition is associated with DPP9 p.Gly167Ser (c.499G>A)?

DPP9 p.Gly167Ser (c.499G>A) is associated with hatipoglu immunodeficiency syndrome (ClinVar).

How common is DPP9 p.Gly167Ser (c.499G>A) in the general population?

DPP9 p.Gly167Ser (c.499G>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about DPP9 p.Gly167Ser (c.499G>A)?

AlphaMissense predicts likely pathogenic (score 0.9735) — an in-silico prediction, not a clinical call.

DPP9 p.Gly167Ser

c.499G>A · rs1193951296 · VCV2499999

Conflicting classifications of pathogenicity No assertion criteria

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9735 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hatipoglu immunodeficiency syndrome

Computational evidence

Protein change
AlphaMissense	0.9735	likely pathogenic
REVEL	0.359	indeterminate
SaProt	LLR -8.15	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 34 kb · p 0.00027 · regional, not allelic
Overall
CADD	28.9	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 G138S vs ClinVar G167S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,898 alleles

Overall 6.84e-05% 1/1,461,658 alleles · very rare

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.Gly167Ser
Coding: c.499G>A
MANE Select: NM_139159
dbSNP: rs1193951296
Type: single nucleotide variant
Location: chr19:4704232 (GRCh38)
Gene constraint: LOEUF 0.647 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.96 · 14 PDB
Residue 167: a UniProt-annotated variant site (in hatis; likely pathogenic); a turn

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-gly167ser (accessed [today's date]).

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