Is DPP6 p.Arg809= (c.2427G>A) pathogenic?

DPP6 p.Arg809= (c.2427G>A) is classified Benign in DPP6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-05-04). Common (popmax 39.9%, eas) — too common for a highly-penetrant pathogenic allele.

DPP6 p.Arg809=

Q: How common is DPP6 p.Arg809= (c.2427G>A) in the general population?

DPP6 p.Arg809= (c.2427G>A) is common (popmax 39.9%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2427G>A · rs1129301 · VCV1246492

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 39.9%, eas) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.3	GERP -1.6, phastCons 1
Overall
CADD	4.958	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 39.9% East Asian · 17,783/44,576 alleles

Filtering AF 39.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 39.2%

Overall 15.6% 250,043/1,607,022 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	39.9%	3
African / African-American	33.9%	3
Ashkenazi Jewishnot grpmax-eligible	21.1%	5
Middle Eastern	18.6%	5
Remaining individualsnot grpmax-eligible	17.8%	6
South Asian	16.4%	6
European (non-Finnish)	13.6%	7
Admixed American	13.4%	7
Amishnot grpmax-eligible	13.4%	7
Finnishnot grpmax-eligible	8.9%	11

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: DPP6
Protein: p.Arg809=
Coding: c.2427G>A
MANE Select: NM_130797
dbSNP: rs1129301
Type: single nucleotide variant
Location: chr7:154889506 (GRCh38)
Gene constraint: LOEUF 0.751 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 87.41 · 8 PDB
Residue 809: a disulfide bond; an α-helix

Full DPP6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPP6 p.Gly65Cys Uncertain significance ★★ ⚠ same type
DPP6 p.Gly65Val Uncertain significance ★★ ⚠ same type
DPP6 p.Lys223Arg Uncertain significance ★★ ⚠ same type
DPP6 p.Pro229Thr Uncertain significance ★★ ⚠ same type
DPP6 c.1261-188G>A Benign ★★ same type
DPP6 c.1261-48G>A Benign ★★ same type
DPP6 c.1299+147A>G Benign ★★ same type
DPP6 c.1299+200A>G 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/dpp6-p-arg809 (accessed [today's date]).

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