Is DPP6 p.Val417Ile (c.1249G>A) pathogenic?

DPP6 p.Val417Ile (c.1249G>A) is classified Uncertain significance in DPP6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-08). AlphaMissense: likely benign (0.0722); Rare (popmax 0.501%, eas); Associated with long QT syndrome.

What condition is associated with DPP6 p.Val417Ile (c.1249G>A)?

DPP6 p.Val417Ile (c.1249G>A) is associated with long QT syndrome (ClinVar).

How common is DPP6 p.Val417Ile (c.1249G>A) in the general population?

DPP6 p.Val417Ile (c.1249G>A) is rare (popmax 0.501%, eas) (gnomAD).

What do computational predictors say about DPP6 p.Val417Ile (c.1249G>A)?

AlphaMissense predicts likely benign (score 0.0722) — an in-silico prediction, not a clinical call.

DPP6 p.Val417Ile

c.1249G>A · rs536301648 · VCV2574031

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0722 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.501%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

long QT syndrome

Computational evidence

Protein change
AlphaMissense	0.0722	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -5.43	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 7.1	GERP 1.6, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 840 kb · p 1.6e-08 · regional, not allelic
Overall
CADD	22.0	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 0.501% East Asian · 224/44,702 alleles

Filtering AF 0.447% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.426%

Overall 0.0153% 246/1,610,186 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.501%	200
South Asian	0.0155%	6,457
Remaining individualsnot grpmax-eligible	0.00481%	20,777
Finnishnot grpmax-eligible	0.00157%	63,592
European (non-Finnish)	0.00034%	294,508

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.Val417Ile
Coding: c.1249G>A
MANE Select: NM_130797
dbSNP: rs536301648
Type: single nucleotide variant
Location: chr7:154794191 (GRCh38)
Gene constraint: LOEUF 0.751 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 87.41 · 8 PDB
Residue 417: a disulfide bond

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

Disease context

long QT syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-val417ile (accessed [today's date]).

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