Is DPP7 p.Val458Met (c.1372G>A) pathogenic?

DPP7 p.Val458Met (c.1372G>A) is classified Uncertain significance in DPP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-04). AlphaMissense: likely pathogenic (0.6807); Ultra-rare (popmax 0.0119%, nfe).

How common is DPP7 p.Val458Met (c.1372G>A) in the general population?

DPP7 p.Val458Met (c.1372G>A) is ultra-rare (popmax 0.0119%, nfe) (gnomAD).

What do computational predictors say about DPP7 p.Val458Met (c.1372G>A)?

AlphaMissense predicts likely pathogenic (score 0.6807) — an in-silico prediction, not a clinical call.

DPP7 p.Val458Met

c.1372G>A · rs142555506 · VCV2300540

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6807 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0119%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6807	likely pathogenic
REVEL	0.467	indeterminate
SaProt	LLR -13.60	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 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	23.4	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 0.0119% European (non-Finnish) · 140/1,179,836 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00964%

Overall 0.00952% 153/1,606,350 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0119%	8,427
African / African-American	0.00801%	12,481
Remaining individualsnot grpmax-eligible	0.00642%	15,586
South Asian	0.0033%	30,332

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.Val458Met
Coding: c.1372G>A
MANE Select: NM_013379
dbSNP: rs142555506
Type: single nucleotide variant
Location: chr9:137110755 (GRCh38)
Gene constraint: LOEUF 1.707 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.44 · 3 PDB
Residue 458: an α-helix

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-val458met (accessed [today's date]).

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