Is DPP7 p.Arg108Leu (c.323G>T) pathogenic?

DPP7 p.Arg108Leu (c.323G>T) is classified Uncertain significance in DPP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-31). AlphaMissense: likely pathogenic (0.9706); Very rare (popmax 0.00135%, sas).

How common is DPP7 p.Arg108Leu (c.323G>T) in the general population?

DPP7 p.Arg108Leu (c.323G>T) is very rare (popmax 0.00135%, sas) (gnomAD).

What do computational predictors say about DPP7 p.Arg108Leu (c.323G>T)?

AlphaMissense predicts likely pathogenic (score 0.9706) — an in-silico prediction, not a clinical call.

DPP7 p.Arg108Leu

c.323G>T · rs763186105 · VCV2553669

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9706 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00135%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9706	likely pathogenic · top 6% in DPP7
REVEL	0.506	indeterminate
SaProt	LLR -13.28	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.1	GERP 1.3, phastCons 1
Regional constraint	o/e 0.41	unconstrained · MANE · 289 bp · p 0.0003 · regional, not allelic
Overall
CADD	33.0	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

Grpmax group 0.00135% South Asian · 1/73,826 alleles

Overall 7.6e-05% 1/1,315,264 alleles · very rare

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: DPP7
Protein: p.Arg108Leu
Coding: c.323G>T
MANE Select: NM_013379
dbSNP: rs763186105
Type: single nucleotide variant
Location: chr9:137114027 (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.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
DPP7 p.Ala158Asp 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-arg108leu (accessed [today's date]).

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