Is DPP6 p.Glu768Asp (c.2304G>C) pathogenic?

DPP6 p.Glu768Asp (c.2304G>C) is classified Uncertain significance in DPP6 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-28). AlphaMissense: likely benign (0.1335); Very rare (popmax 0.00167%, amr); Associated with intellectual disability, autosomal dominant 33.

What condition is associated with DPP6 p.Glu768Asp (c.2304G>C)?

DPP6 p.Glu768Asp (c.2304G>C) is associated with intellectual disability, autosomal dominant 33 (ClinVar).

How common is DPP6 p.Glu768Asp (c.2304G>C) in the general population?

DPP6 p.Glu768Asp (c.2304G>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DPP6 p.Glu768Asp (c.2304G>C)?

AlphaMissense predicts likely benign (score 0.1335) — an in-silico prediction, not a clinical call.

DPP6 p.Glu768Asp

c.2304G>C · rs1584993945 · VCV802384

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1335 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability, autosomal dominant 33

Computational evidence

Protein change
AlphaMissense	0.1335	likely benign
REVEL	0.076	moderately benign-leaning
SaProt	LLR -6.39	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.85	donor loss · deltas
Pangolin	Δ0.68	loss · gain 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 9.6	GERP 1.4, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 840 kb · p 1.6e-08 · regional, not allelic
Overall
CADD	31.0	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 0.00167% Admixed American · 1/59,994 alleles

Overall 6.2e-05% 1/1,613,626 alleles · very rare exomes 0/1,461,440 · genomes 1/152,186 · joint denominator

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.Glu768Asp
Coding: c.2304G>C
MANE Select: NM_130797
dbSNP: rs1584993945
Type: single nucleotide variant
Location: chr7:154887734 (GRCh38)
Gene constraint: LOEUF 0.751 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 87.41 · 8 PDB
Residue 768: a turn

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.Glu768Lys Uncertain significance ★ ⚠ same residue
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

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-glu768asp (accessed [today's date]).

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