Is DPP4 p.Gln247Pro (c.740A>C) pathogenic?

DPP4 p.Gln247Pro (c.740A>C) is classified Uncertain significance in DPP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-26). AlphaMissense: likely benign (0.2256); Rare (popmax 0.132%, sas).

How common is DPP4 p.Gln247Pro (c.740A>C) in the general population?

DPP4 p.Gln247Pro (c.740A>C) is rare (popmax 0.132%, sas) (gnomAD).

What do computational predictors say about DPP4 p.Gln247Pro (c.740A>C)?

AlphaMissense predicts likely benign (score 0.2256) — an in-silico prediction, not a clinical call.

DPP4 p.Gln247Pro

c.740A>C · rs201266487 · VCV2556597

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2256 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.132%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2256	likely benign
REVEL	0.482	indeterminate
SaProt	LLR -7.54	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.7, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 81 kb · p 0.82 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.132% South Asian · 120/91,082 alleles

Filtering AF 0.113% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.105%

Overall 0.00818% 132/1,613,946 alleles · rare exomes 117/1,461,734 · genomes 15/152,212 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.132%	759
Middle Eastern	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.0032%	31,242
European (non-Finnish)	0.000763%	131,106

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.Gln247Pro
Coding: c.740A>C
MANE Select: NM_001935
dbSNP: rs201266487
Type: single nucleotide variant
Location: chr2:162035198 (GRCh38)
Gene constraint: LOEUF 0.901 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.45 · 121 PDB

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-gln247pro (accessed [today's date]).

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