Is DPP4 p.Ala16= (c.48G>A) pathogenic?

DPP4 p.Ala16= (c.48G>A) is classified Benign in DPP4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). Rare (popmax 0.419%, nfe).

How common is DPP4 p.Ala16= (c.48G>A) in the general population?

DPP4 p.Ala16= (c.48G>A) is rare (popmax 0.419%, nfe) (gnomAD).

DPP4 p.Ala16=

c.48G>A · rs148524083 · VCV780024

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.419%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.8	GERP -2.5
Overall
CADD	16.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.419% European (non-Finnish) · 4,940/1,180,024 alleles

Filtering AF 0.409% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.405%

Overall 0.341% 5,506/1,614,082 alleles · rare exomes 5,206/1,461,764 · genomes 300/152,318 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.483%	207
European (non-Finnish)grpmax	0.419%	239
Remaining individualsnot grpmax-eligible	0.272%	368
Admixed American	0.0533%	1,876
African / African-American	0.0453%	2,207
Ashkenazi Jewishnot grpmax-eligible	0.0203%	4,935
Middle Eastern	0.0167%	5,984
South Asian	0.0154%	6,505

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala16=
Coding: c.48G>A
MANE Select: NM_001935
dbSNP: rs148524083
Type: single nucleotide variant
Location: chr2:162073445 (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.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
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-ala16 (accessed [today's date]).

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