Is DPP6 p.Ala778= (c.2334G>A) pathogenic?

DPP6 p.Ala778= (c.2334G>A) is classified Likely benign in DPP6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-25). Very rare (popmax 0.00339%, nfe); Associated with DPP6-related disorder.

What condition is associated with DPP6 p.Ala778= (c.2334G>A)?

DPP6 p.Ala778= (c.2334G>A) is associated with DPP6-related disorder (ClinVar).

How common is DPP6 p.Ala778= (c.2334G>A) in the general population?

DPP6 p.Ala778= (c.2334G>A) is very rare (popmax 0.00339%, nfe) (gnomAD).

DPP6 p.Ala778=

c.2334G>A · rs766943750 · VCV3043455

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00339%, nfe)

Conditions

DPP6-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.8	GERP -2.6
Overall
CADD	0.261	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00339% European (non-Finnish) · 40/1,179,700 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00225%

Overall 0.00279% 45/1,612,838 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,815
European (non-Finnish)grpmax	0.00339%	29,493
East Asian	0.00223%	44,878
African / African-American	0.00134%	74,800

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala778=
Coding: c.2334G>A
MANE Select: NM_130797
dbSNP: rs766943750
Type: single nucleotide variant
Location: chr7:154889301 (GRCh38)
Gene constraint: LOEUF 0.751 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 87.41 · 8 PDB
Residue 778: a disulfide bond

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

Disease context

DPP6-related disorder

Similar variants

DPP6 p.Ala778Thr Likely benign same residue
DPP6 p.Ala778Val Likely benign ⚠ same residue
DPP6 c.1299+68G>A Uncertain significance ★ same condition
DPP6 c.244-1G>A Uncertain significance ★ same condition
DPP6 p.Glu139Lys Uncertain significance ⚠ same condition
DPP6 p.His267Leu Uncertain significance ⚠ same condition
DPP6 p.Tyr205Asn Uncertain significance ⚠ same condition
DPP6 c.1299+179C>G Likely benign 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-ala778 (accessed [today's date]).

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