Is DPP6 p.Ala778Val (c.2333C>T) pathogenic?

DPP6 p.Ala778Val (c.2333C>T) is classified Likely benign in DPP6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-04-27). AlphaMissense: likely benign (0.0738); Rare (popmax 0.1%, amr); Associated with DPP6-related disorder.

What condition is associated with DPP6 p.Ala778Val (c.2333C>T)?

DPP6 p.Ala778Val (c.2333C>T) is associated with DPP6-related disorder (ClinVar).

How common is DPP6 p.Ala778Val (c.2333C>T) in the general population?

DPP6 p.Ala778Val (c.2333C>T) is rare (popmax 0.1%, amr) (gnomAD).

What do computational predictors say about DPP6 p.Ala778Val (c.2333C>T)?

AlphaMissense predicts likely benign (score 0.0738) — an in-silico prediction, not a clinical call.

DPP6 p.Ala778Val

c.2333C>T · rs201710106 · VCV3051723

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0738 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.1%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DPP6-related disorder

Computational evidence

Protein change
AlphaMissense	0.0738	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -8.73	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 0.35	GERP -2
Regional constraint	o/e 0.83	unconstrained · MANE · 840 kb · p 1.6e-08 · regional, not allelic
Overall
CADD	10.86	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 0.1% Admixed American · 60/59,904 alleles

Filtering AF 0.0799% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0725%

Overall 0.00874% 141/1,613,068 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.1%	998
East Asian	0.0178%	5,608
African / African-American	0.0147%	6,813
Remaining individualsnot grpmax-eligible	0.0128%	7,808
South Asian	0.00441%	22,666
European (non-Finnish)	0.00424%	23,594

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.Ala778Val
Coding: c.2333C>T
MANE Select: NM_130797
dbSNP: rs201710106
Type: single nucleotide variant
Location: chr7:154889300 (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.Ala778Thr 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-ala778val (accessed [today's date]).

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