Is DPP7 p.Gly440Arg (c.1318G>C) pathogenic?

DPP7 p.Gly440Arg (c.1318G>C) is classified Uncertain significance in DPP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-18). AlphaMissense: ambiguous (0.5081); Ultra-rare (popmax 0.0267%, amr).

How common is DPP7 p.Gly440Arg (c.1318G>C) in the general population?

DPP7 p.Gly440Arg (c.1318G>C) is ultra-rare (popmax 0.0267%, amr) (gnomAD).

What do computational predictors say about DPP7 p.Gly440Arg (c.1318G>C)?

AlphaMissense predicts ambiguous (score 0.5081) — an in-silico prediction, not a clinical call.

DPP7 p.Gly440Arg

c.1318G>C · rs777774924 · VCV2510097

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5081 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5081	ambiguous
REVEL	0.654	pathogenic-leaning
SaProt	LLR -9.39	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 5.6	GERP 1.3, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 3,355 bp · p 5.6e-05 · regional, not allelic
Overall
CADD	22.0	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 0.0267% Admixed American · 16/59,980 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00446% 72/1,612,872 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0267%	3,749
European (non-Finnish)	0.00424%	23,599
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,596
East Asian	0.00223%	44,878
South Asian	0.0022%	45,528
Finnishnot grpmax-eligible	0.00159%	63,052
African / African-American	0.00133%	74,912

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.Gly440Arg
Coding: c.1318G>C
MANE Select: NM_013379
dbSNP: rs777774924
Type: single nucleotide variant
Location: chr9:137110905 (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-gly440arg (accessed [today's date]).

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