Is DPP6 p.Ala778Thr (c.2332G>A) pathogenic?

DPP6 p.Ala778Thr (c.2332G>A) is classified Likely benign in DPP6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-06). AlphaMissense: likely benign (0.0668); Rare (popmax 0.199%, nfe); Associated with DPP6-related disorder.

What condition is associated with DPP6 p.Ala778Thr (c.2332G>A)?

DPP6 p.Ala778Thr (c.2332G>A) is associated with DPP6-related disorder (ClinVar).

How common is DPP6 p.Ala778Thr (c.2332G>A) in the general population?

DPP6 p.Ala778Thr (c.2332G>A) is rare (popmax 0.199%, nfe) (gnomAD).

What do computational predictors say about DPP6 p.Ala778Thr (c.2332G>A)?

AlphaMissense predicts likely benign (score 0.0668) — an in-silico prediction, not a clinical call.

DPP6 p.Ala778Thr

c.2332G>A · rs188276022 · VCV3038014

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0668 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.199%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DPP6-related disorder

Computational evidence

Protein change
AlphaMissense	0.0668	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -7.14	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 0.19	GERP -2.1
Regional constraint	o/e 0.83	unconstrained · MANE · 840 kb · p 1.6e-08 · regional, not allelic
Overall
CADD	10.87	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.199% European (non-Finnish) · 2,350/1,179,708 alleles

Filtering AF 0.192% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.19%

Overall 0.174% 2,800/1,612,960 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	1.1%	91
Ashkenazi Jewishnot grpmax-eligible	0.663%	151
European (non-Finnish)grpmax	0.199%	502
Remaining individualsnot grpmax-eligible	0.186%	539
Admixed American	0.125%	798
Middle Eastern	0.066%	1,516
African / African-American	0.0334%	2,996
South Asian	0.0199%	5,037
East Asian	0.0134%	7,476

Amish 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.Ala778Thr
Coding: c.2332G>A
MANE Select: NM_130797
dbSNP: rs188276022
Type: single nucleotide variant
Location: chr7:154889299 (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.Ala778= 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-ala778thr (accessed [today's date]).

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