Is DPP9 p.Asn866Asp (c.2596A>G) pathogenic?

DPP9 p.Asn866Asp (c.2596A>G) is classified Uncertain significance in DPP9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-24). AlphaMissense: ambiguous (0.3713); Very rare (popmax 0.000255%, nfe).

How common is DPP9 p.Asn866Asp (c.2596A>G) in the general population?

DPP9 p.Asn866Asp (c.2596A>G) is very rare (popmax 0.000255%, nfe) (gnomAD).

What do computational predictors say about DPP9 p.Asn866Asp (c.2596A>G)?

AlphaMissense predicts ambiguous (score 0.3713) — an in-silico prediction, not a clinical call.

DPP9 p.Asn866Asp

c.2596A>G · VCV4014649

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3713 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000255%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3713	ambiguous
REVEL	0.198	benign-leaning
SaProt	LLR -5.52	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP -3.6, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 8,223 bp · p 2e-05 · regional, not allelic
Overall
CADD	27.5	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 N837D vs ClinVar N866D) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000255% European (non-Finnish) · 3/1,175,092 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000207% 3/1,451,278 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.Asn866Asp
Coding: c.2596A>G
MANE Select: NM_139159
Type: single nucleotide variant
Location: chr19:4676647 (GRCh38)
Gene constraint: LOEUF 0.647 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.96 · 14 PDB

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

Similar variants

DPP9 p.Asp310Asn Uncertain significance ★★ ⚠ same type
DPP9 p.Lys509Arg Uncertain significance ★★ ⚠ same type
DPP9 p.Thr301Met Uncertain significance ★★ ⚠ same type
DPP9 p.Ala184Gly Benign/Likely benign ★★ same type
DPP9 p.Glu566Lys Benign/Likely benign ★★ ⚠ same type
DPP9 p.His83= Benign/Likely benign ★★ same type
DPP9 p.Pro322= Benign ★★ same type
DPP9 p.Ser236Asn Likely benign ★★ same type

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-asn866asp (accessed [today's date]).

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