Is DPP4 p.Tyr752His (c.2254T>C) pathogenic?

DPP4 p.Tyr752His (c.2254T>C) is classified Uncertain significance in DPP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-27). AlphaMissense: ambiguous (0.4669); Absent from gnomAD v4.1.

How common is DPP4 p.Tyr752His (c.2254T>C) in the general population?

DPP4 p.Tyr752His (c.2254T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DPP4 p.Tyr752His (c.2254T>C)?

AlphaMissense predicts ambiguous (score 0.4669) — an in-silico prediction, not a clinical call.

DPP4 p.Tyr752His

c.2254T>C · rs2468418888 · VCV3085548

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4669 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4669	ambiguous
REVEL	0.626	indeterminate
SaProt	LLR -10.32	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.8, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 81 kb · p 0.82 · regional, not allelic
Overall
CADD	26.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DPP4
Protein: p.Tyr752His
Coding: c.2254T>C
MANE Select: NM_001935
dbSNP: rs2468418888
Type: single nucleotide variant
Location: chr2:161993330 (GRCh38)
Gene constraint: LOEUF 0.901 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.45 · 121 PDB
Residue 752: an α-helix; a disulfide bond

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.Val266Ile Likely benign ★★ ⚠ same type
DPP4 p.Ala654Thr 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-tyr752his (accessed [today's date]).

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