Is DPP7 p.Ser186Arg (c.556A>C) pathogenic?

DPP7 p.Ser186Arg (c.556A>C) is classified Uncertain significance in DPP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-01). AlphaMissense: likely pathogenic (0.9926); Absent from gnomAD v4.1.

How common is DPP7 p.Ser186Arg (c.556A>C) in the general population?

DPP7 p.Ser186Arg (c.556A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DPP7 p.Ser186Arg (c.556A>C)?

AlphaMissense predicts likely pathogenic (score 0.9926) — an in-silico prediction, not a clinical call.

DPP7 p.Ser186Arg

c.556A>C · rs2538473599 · VCV2331507

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9926 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9926	likely pathogenic · top 1% in DPP7
REVEL	0.673	pathogenic-leaning
SaProt	LLR -13.97	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.5, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 3,355 bp · p 5.6e-05 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DPP7
Protein: p.Ser186Arg
Coding: c.556A>C
MANE Select: NM_013379
dbSNP: rs2538473599
Type: single nucleotide variant
Location: chr9:137113426 (GRCh38)
Gene constraint: LOEUF 1.707 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.44 · 3 PDB

Full DPP7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPP7 p.Ser186Thr Uncertain significance ★ ⚠ same residue
DPP7 p.Arg17= Likely benign ★★ same type
DPP7 c.322-1G>T Uncertain significance ★ same type
DPP7 p.Ala118Gly Uncertain significance ★ ⚠ same type
DPP7 p.Ala118Val Uncertain significance ★ ⚠ same type
DPP7 p.Ala136Val Uncertain significance ★ ⚠ same type
DPP7 p.Ala139Gly Uncertain significance ★ ⚠ same type
DPP7 p.Ala13Val 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/dpp7-p-ser186arg (accessed [today's date]).

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