Is DPP7 p.Glu376Lys (c.1126G>A) pathogenic?

DPP7 p.Glu376Lys (c.1126G>A) is classified Uncertain significance in DPP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-09). AlphaMissense: likely benign (0.109); Very rare (popmax 0.0022%, nfe).

How common is DPP7 p.Glu376Lys (c.1126G>A) in the general population?

DPP7 p.Glu376Lys (c.1126G>A) is very rare (popmax 0.0022%, nfe) (gnomAD).

What do computational predictors say about DPP7 p.Glu376Lys (c.1126G>A)?

AlphaMissense predicts likely benign (score 0.109) — an in-silico prediction, not a clinical call.

DPP7 p.Glu376Lys

c.1126G>A · VCV3842290

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.109 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.109	likely benign
REVEL	0.141	moderately benign-leaning
SaProt	LLR -9.12	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 0.014	GERP -2.3
Regional constraint	o/e 1.17	unconstrained · MANE · 3,355 bp · p 5.6e-05 · regional, not allelic
Overall
CADD	5.914	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0022% European (non-Finnish) · 26/1,179,498 alleles

Filtering AF 0.00153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.0018% 29/1,612,858 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0022%	45,365
South Asian	0.0022%	45,528
African / African-American	0.00134%	74,800

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.Glu376Lys
Coding: c.1126G>A
MANE Select: NM_013379
Type: single nucleotide variant
Location: chr9:137111954 (GRCh38)
Gene constraint: LOEUF 1.707 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.44 · 3 PDB
Residue 376: an α-helix

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

Similar variants

DPP7 p.Glu376Asp 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-glu376lys (accessed [today's date]).

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