Is DPP6 c.2245+285G>A pathogenic?

DPP6 c.2245+285G>A is classified Benign in DPP6 (ClinVar, Single submitter, 2 submitters; last evaluated 2021-06-19). Common (popmax 6.09%, eas) — too common for a highly-penetrant pathogenic allele.

DPP6 c.2245+285G>A

Q: How common is DPP6 c.2245+285G>A in the general population?

DPP6 c.2245+285G>A is common (popmax 6.09%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs79782991 · VCV1246988

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 6.09%, 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
Splice region	donor +285	deep intronic (+285 nt into the intron)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.85	GERP -2.3
Overall
CADD	0.457	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.09% East Asian · 315/5,174 alleles

Filtering AF 5.54% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.32%

Overall 3.29% 5,006/152,350 alleles · common

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	7.59%	13
East Asiangrpmax	6.09%	16
Ashkenazi Jewishnot grpmax-eligible	5.07%	20
Remaining individualsnot grpmax-eligible	4.44%	23
Middle Eastern	4.42%	23
European (non-Finnish)	3.91%	26
Admixed American	3.29%	30
South Asian	1.66%	60
African / African-American	0.854%	117
Amishnot grpmax-eligible	0.11%	912

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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
Coding: c.2245+285G>A
MANE Select: NM_130797
dbSNP: rs79782991
Type: single nucleotide variant
Location: chr7:154886029 (GRCh38)
Gene constraint: LOEUF 0.751 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 87.41 · 8 PDB

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-c-2245-plus-285g-a (accessed [today's date]).

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