Is DPP4 p.Ser437Thr (c.1310G>C) pathogenic?

DPP4 p.Ser437Thr (c.1310G>C) is classified Benign in DPP4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.0769); Low-frequency (popmax 3.42%, afr).

How common is DPP4 p.Ser437Thr (c.1310G>C) in the general population?

DPP4 p.Ser437Thr (c.1310G>C) is low-frequency (popmax 3.42%, afr) (gnomAD).

What do computational predictors say about DPP4 p.Ser437Thr (c.1310G>C)?

AlphaMissense predicts likely benign (score 0.0769) — an in-silico prediction, not a clinical call.

DPP4 p.Ser437Thr

c.1310G>C · rs1129599 · VCV787775

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0769 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.42%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0769	likely benign
REVEL	0.21	benign-leaning
SaProt	LLR -7.58	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 -5.2
Regional constraint	o/e 1.01	unconstrained · MANE · 81 kb · p 0.82 · regional, not allelic
Overall
CADD	1.029	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 3.42% African / African-American · 2,562/75,004 alleles

Filtering AF 3.31% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.26%

Overall 0.179% 2,894/1,613,986 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.42%	29
Admixed American	0.248%	403
Remaining individualsnot grpmax-eligible	0.213%	470
Middle Eastern	0.0825%	1,212
South Asian	0.00659%	15,169
European (non-Finnish)	0.00331%	30,257

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.Ser437Thr
Coding: c.1310G>C
MANE Select: NM_001935
dbSNP: rs1129599
Type: single nucleotide variant
Location: chr2:162018839 (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.Val266Ile Likely 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-ser437thr (accessed [today's date]).

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