Is DPP4 p.Ser108Ala (c.322T>G) pathogenic?

DPP4 p.Ser108Ala (c.322T>G) is classified Uncertain significance in DPP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-28). AlphaMissense: ambiguous (0.4296); Very rare (popmax 0.00526%, nfe).

How common is DPP4 p.Ser108Ala (c.322T>G) in the general population?

DPP4 p.Ser108Ala (c.322T>G) is very rare (popmax 0.00526%, nfe) (gnomAD).

What do computational predictors say about DPP4 p.Ser108Ala (c.322T>G)?

AlphaMissense predicts ambiguous (score 0.4296) — an in-silico prediction, not a clinical call.

DPP4 p.Ser108Ala

c.322T>G · VCV4014620

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4296 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00526%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4296	ambiguous
REVEL	0.858	moderately pathogenic-leaning
SaProt	LLR -9.90	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 81 kb · p 0.82 · regional, not allelic
Overall
CADD	25.8	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 0.00526% European (non-Finnish) · 62/1,179,068 alleles

Filtering AF 0.00419% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00391% 63/1,612,718 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00526%	19,017
Admixed American	0.00167%	59,852

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.Ser108Ala
Coding: c.322T>G
MANE Select: NM_001935
Type: single nucleotide variant
Location: chr2:162045576 (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-ser108ala (accessed [today's date]).

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