Is DPP4 p.His345Arg (c.1034A>G) pathogenic?

DPP4 p.His345Arg (c.1034A>G) is classified Uncertain significance in DPP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-17). AlphaMissense: likely benign (0.106); Very rare (popmax 0.00167%, amr).

How common is DPP4 p.His345Arg (c.1034A>G) in the general population?

DPP4 p.His345Arg (c.1034A>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DPP4 p.His345Arg (c.1034A>G)?

AlphaMissense predicts likely benign (score 0.106) — an in-silico prediction, not a clinical call.

DPP4 p.His345Arg

c.1034A>G · rs748931174 · VCV2326729

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.106 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.106	likely benign
REVEL	0.23	benign-leaning
SaProt	LLR -2.28	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 1.1	GERP -2, phastCons 0.88
Regional constraint	o/e 1.01	unconstrained · MANE · 81 kb · p 0.82 · regional, not allelic
Overall
CADD	12.67	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 0.00167% Admixed American · 1/60,006 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.000991% 16/1,613,914 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,006
European (non-Finnish)	0.00127%	78,666

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.His345Arg
Coding: c.1034A>G
MANE Select: NM_001935
dbSNP: rs748931174
Type: single nucleotide variant
Location: chr2:162022789 (GRCh38)
Gene constraint: LOEUF 0.901 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.45 · 121 PDB
Residue 345: 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.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-his345arg (accessed [today's date]).

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