Is DPP4 p.Val266Ile (c.796G>A) pathogenic?

DPP4 p.Val266Ile (c.796G>A) is classified Likely benign in DPP4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.116); Rare (popmax 0.727%, nfe).

How common is DPP4 p.Val266Ile (c.796G>A) in the general population?

DPP4 p.Val266Ile (c.796G>A) is rare (popmax 0.727%, nfe) (gnomAD).

What do computational predictors say about DPP4 p.Val266Ile (c.796G>A)?

AlphaMissense predicts likely benign (score 0.116) — an in-silico prediction, not a clinical call.

DPP4 p.Val266Ile

c.796G>A · rs56179129 · VCV770342

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.116 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.727%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.116	likely benign
REVEL	0.169	moderately benign-leaning
SaProt	LLR -9.19	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 3.4	GERP 1.7, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 81 kb · p 0.82 · regional, not allelic
Overall
CADD	20.2	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 0.727% European (non-Finnish) · 8,563/1,177,840 alleles

Filtering AF 0.714% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.709%

Overall 0.576% 9,269/1,608,642 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.727%	138
Remaining individualsnot grpmax-eligible	0.464%	215
Admixed American	0.403%	248
Middle Eastern	0.265%	377
African / African-American	0.159%	629
South Asian	0.0298%	3,353
Ashkenazi Jewishnot grpmax-eligible	0.0203%	4,915
Finnishnot grpmax-eligible	0.0158%	6,328

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: DPP4
Protein: p.Val266Ile
Coding: c.796G>A
MANE Select: NM_001935
dbSNP: rs56179129
Type: single nucleotide variant
Location: chr2:162033632 (GRCh38)
Gene constraint: LOEUF 0.901 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.45 · 121 PDB
Residue 266: a UniProt-annotated variant site (in); a β-strand

Full DPP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPP4 c.1987+4T>C Benign ★★ same type
DPP4 p.Ala16= Benign ★★ same type
DPP4 p.Gly645= Benign ★★ same type
DPP4 p.Leu27= Benign ★★ same type
DPP4 p.Lys539= Likely benign ★★ same type
DPP4 p.Ser437Thr Benign ★★ same type
DPP4 p.Ala654Thr Uncertain significance ★ ⚠ same type
DPP4 p.Ala81Thr Uncertain significance ★ ⚠ same type

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/dpp4-p-val266ile (accessed [today's date]).

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