Is DPP9 p.Val819Met (c.2455G>A) pathogenic?

DPP9 p.Val819Met (c.2455G>A) is classified Uncertain significance in DPP9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-22). AlphaMissense: likely pathogenic (0.647); Very rare (popmax 0.00224%, eas).

How common is DPP9 p.Val819Met (c.2455G>A) in the general population?

DPP9 p.Val819Met (c.2455G>A) is very rare (popmax 0.00224%, eas) (gnomAD).

What do computational predictors say about DPP9 p.Val819Met (c.2455G>A)?

AlphaMissense predicts likely pathogenic (score 0.647) — an in-silico prediction, not a clinical call.

DPP9 p.Val819Met

c.2455G>A · VCV4662004

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.647 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.647	likely pathogenic
REVEL	0.314	indeterminate
SaProt	LLR -11.08	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, 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

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V790M vs ClinVar V819M) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00224% East Asian · 1/44,722 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000373% 6/1,609,768 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00224%	44,722
African / African-American	0.00133%	75,004
European (non-Finnish)	0.000339%	294,586

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.Val819Met
Coding: c.2455G>A
MANE Select: NM_139159
Type: single nucleotide variant
Location: chr19:4682715 (GRCh38)
Gene constraint: LOEUF 0.647 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.96 · 14 PDB
Residue 819: 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-val819met (accessed [today's date]).

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