Is DPP9 p.Glu566Lys (c.1696G>A) pathogenic?

DPP9 p.Glu566Lys (c.1696G>A) is classified Benign/Likely benign in DPP9 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-04-01). AlphaMissense: likely benign (0.0906); Rare (popmax 0.522%, mid).

How common is DPP9 p.Glu566Lys (c.1696G>A) in the general population?

DPP9 p.Glu566Lys (c.1696G>A) is rare (popmax 0.522%, mid) (gnomAD).

What do computational predictors say about DPP9 p.Glu566Lys (c.1696G>A)?

AlphaMissense predicts likely benign (score 0.0906) — an in-silico prediction, not a clinical call.

DPP9 p.Glu566Lys

c.1696G>A · rs200229921 · VCV717743

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0906 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.522%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0906	likely benign
REVEL	0.14	moderately benign-leaning
SaProt	LLR -8.50	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 34 kb · p 0.00027 · regional, not allelic
Overall
CADD	23.6	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 E537K vs ClinVar E566K) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.522% Middle Eastern · 31/5,938 alleles

Filtering AF 0.412% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.408%

Overall 0.339% 5,323/1,572,348 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.522%	192
European (non-Finnish)	0.422%	237
Remaining individualsnot grpmax-eligible	0.22%	455
Admixed American	0.182%	549
Ashkenazi Jewishnot grpmax-eligible	0.135%	739
African / African-American	0.0823%	1,215
South Asian	0.0573%	1,745
Finnishnot grpmax-eligible	0.0332%	3,009
East Asian	0.00472%	21,207

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.Glu566Lys
Coding: c.1696G>A
MANE Select: NM_139159
dbSNP: rs200229921
Type: single nucleotide variant
Location: chr19:4689623 (GRCh38)
Gene constraint: LOEUF 0.647 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.96 · 14 PDB
Residue 566: a UniProt-annotated variant site (in hatis; likely pathogenic); a β-strand

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.His83= Benign/Likely benign ★★ same type
DPP9 p.Pro322= Benign ★★ same type
DPP9 p.Ser236Asn Likely benign ★★ same type
DPP9 p.Thr329Met 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-glu566lys (accessed [today's date]).

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