Is DPP6 p.Gln526His (c.1578G>C) pathogenic?

DPP6 p.Gln526His (c.1578G>C) is classified Uncertain significance in DPP6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-29). AlphaMissense: likely benign (0.1468); Very rare (popmax 0.00668%, eas); Associated with intellectual disability, autosomal dominant 33.

What condition is associated with DPP6 p.Gln526His (c.1578G>C)?

DPP6 p.Gln526His (c.1578G>C) is associated with intellectual disability, autosomal dominant 33, ventricular fibrillation, paroxysmal familial, 2 (ClinVar).

How common is DPP6 p.Gln526His (c.1578G>C) in the general population?

DPP6 p.Gln526His (c.1578G>C) is very rare (popmax 0.00668%, eas) (gnomAD).

What do computational predictors say about DPP6 p.Gln526His (c.1578G>C)?

AlphaMissense predicts likely benign (score 0.1468) — an in-silico prediction, not a clinical call.

DPP6 p.Gln526His

c.1578G>C · VCV3594441

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1468 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability, autosomal dominant 33

Computational evidence

Protein change
AlphaMissense	0.1468	likely benign
REVEL	0.14	moderately benign-leaning
SaProt	LLR -7.83	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 1.6	GERP -1.4, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 840 kb · p 1.6e-08 · regional, not allelic
Overall
CADD	22.6	PHRED · no single calibrated threshold — expert panels disagree

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

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% East Asian · 3/44,878 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000205% 3/1,461,556 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.Gln526His
Coding: c.1578G>C
MANE Select: NM_130797
Type: single nucleotide variant
Location: chr7:154807024 (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

Disease context

intellectual disability, autosomal dominant 33 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ventricular fibrillation, paroxysmal familial, 2

Similar variants

DPP6 p.Lys223Arg Uncertain significance ★★ ⚠ same condition
DPP6 p.Pro229Thr Uncertain significance ★★ ⚠ same condition
DPP6 p.Gln271= Benign ★★ same condition
DPP6 p.Lys241= Benign ★★ same condition
DPP6 p.Arg775Ter Likely pathogenic ★ same condition
DPP6 p.Tyr205Ter Likely pathogenic ★ same condition
DPP6 c.1667-4A>G Uncertain significance ★ same condition
DPP6 c.2304+2T>C Uncertain significance ★ same condition

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-gln526his (accessed [today's date]).

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