Is DPP6 p.Met1Ile (c.3G>A) pathogenic?

DPP6 p.Met1Ile (c.3G>A) is classified Uncertain significance in DPP6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-17). Absent from gnomAD v4.1; Associated with intellectual disability, autosomal dominant 33.

What condition is associated with DPP6 p.Met1Ile (c.3G>A)?

DPP6 p.Met1Ile (c.3G>A) is associated with intellectual disability, autosomal dominant 33 (ClinVar).

How common is DPP6 p.Met1Ile (c.3G>A) in the general population?

DPP6 p.Met1Ile (c.3G>A) is absent from gnomAD v4.1 (gnomAD).

DPP6 p.Met1Ile

c.3G>A · rs2486020218 · VCV2627608

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

start-loss

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

intellectual disability, autosomal dominant 33

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function
REVEL	0.421	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9	GERP 2.9, phastCons 1
Overall
CADD	25.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DPP6
Protein: p.Met1Ile
Coding: c.3G>A
MANE Select: NM_130797
dbSNP: rs2486020218
Type: single nucleotide variant
Location: chr7:154052823 (GRCh38)
Gene constraint: LOEUF 0.751 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 87.41 · 8 PDB
Residue 1: the 'disordered' region

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

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.2304+2T>C Uncertain significance ★ same condition
DPP6 c.457+3G>A 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-met1ile (accessed [today's date]).

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