Is DPP6 p.Pro364Arg (c.1091C>G) pathogenic?

DPP6 p.Pro364Arg (c.1091C>G) is classified Uncertain significance in DPP6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2017-07-14). AlphaMissense: ambiguous (0.55); Very rare (popmax 0.000763%, nfe); Associated with Wolff-Parkinson-White syndrome.

What condition is associated with DPP6 p.Pro364Arg (c.1091C>G)?

DPP6 p.Pro364Arg (c.1091C>G) is associated with Wolff-Parkinson-White syndrome (ClinVar).

How common is DPP6 p.Pro364Arg (c.1091C>G) in the general population?

DPP6 p.Pro364Arg (c.1091C>G) is very rare (popmax 0.000763%, nfe) (gnomAD).

What do computational predictors say about DPP6 p.Pro364Arg (c.1091C>G)?

AlphaMissense predicts ambiguous (score 0.55) — an in-silico prediction, not a clinical call.

DPP6 p.Pro364Arg

c.1091C>G · rs756673341 · VCV487598

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.55 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

Conditions

Wolff-Parkinson-White syndrome

Computational evidence

Protein change
AlphaMissense	0.55	ambiguous
REVEL	0.414	indeterminate
SaProt	LLR -7.13	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.6, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 840 kb · p 1.6e-08 · regional, not allelic
Overall
CADD	26.9	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000763% European (non-Finnish) · 9/1,179,550 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000616% 9/1,461,078 alleles · very rare

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.Pro364Arg
Coding: c.1091C>G
MANE Select: NM_130797
dbSNP: rs756673341
Type: single nucleotide variant
Location: chr7:154772897 (GRCh38)
Gene constraint: LOEUF 0.751 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 87.41 · 8 PDB
Residue 364: a β-strand

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

Disease context

Wolff-Parkinson-White syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DPP6 p.Met385Thr Uncertain significance ⚠ same condition
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

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-pro364arg (accessed [today's date]).

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