Is DPP9 p.Glu736Ala (c.2207A>C) pathogenic?

DPP9 p.Glu736Ala (c.2207A>C) is classified Uncertain significance in DPP9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-29). AlphaMissense: ambiguous (0.3718); Absent from gnomAD v4.1.

How common is DPP9 p.Glu736Ala (c.2207A>C) in the general population?

DPP9 p.Glu736Ala (c.2207A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DPP9 p.Glu736Ala (c.2207A>C)?

AlphaMissense predicts ambiguous (score 0.3718) — an in-silico prediction, not a clinical call.

DPP9 p.Glu736Ala

c.2207A>C · VCV4014658

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3718 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.3718	ambiguous
REVEL	0.374	indeterminate
SaProt	LLR -10.66	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 8,223 bp · p 2e-05 · regional, not allelic
Overall
CADD	28.2	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 E707A vs ClinVar E736A) — 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.Glu736Ala
Coding: c.2207A>C
MANE Select: NM_139159
Type: single nucleotide variant
Location: chr19:4683601 (GRCh38)
Gene constraint: LOEUF 0.647 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.96 · 14 PDB
Residue 736: a UniProt-annotated variant site (in hatis; likely pathogenic); an α-helix

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-glu736ala (accessed [today's date]).

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