Is DPP7 p.Phe72Ile (c.214T>A) pathogenic?

DPP7 p.Phe72Ile (c.214T>A) is classified Uncertain significance in DPP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-08). AlphaMissense: ambiguous (0.563); Very rare (popmax 0.00502%, amr).

How common is DPP7 p.Phe72Ile (c.214T>A) in the general population?

DPP7 p.Phe72Ile (c.214T>A) is very rare (popmax 0.00502%, amr) (gnomAD).

What do computational predictors say about DPP7 p.Phe72Ile (c.214T>A)?

AlphaMissense predicts ambiguous (score 0.563) — an in-silico prediction, not a clinical call.

DPP7 p.Phe72Ile

c.214T>A · rs755136780 · VCV3085557

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.563 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00502%, amr)

Computational evidence

Protein change
AlphaMissense	0.563	ambiguous
REVEL	0.366	indeterminate
SaProt	LLR -12.98	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.2, phastCons 1
Regional constraint	o/e 1.35	unconstrained · MANE · 416 bp · p 8.2e-05 · regional, not allelic
Overall
CADD	27.4	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 0.00502% Admixed American · 3/59,744 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000669%

Overall 0.00056% 9/1,605,826 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00502%	19,915
Finnishnot grpmax-eligible	0.00161%	62,112
South Asian	0.00111%	90,386
European (non-Finnish)	0.00034%	294,287

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.Phe72Ile
Coding: c.214T>A
MANE Select: NM_013379
dbSNP: rs755136780
Type: single nucleotide variant
Location: chr9:137114350 (GRCh38)
Gene constraint: LOEUF 1.707 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.44 · 3 PDB
Residue 72: a β-strand

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

Similar variants

DPP7 p.Phe72Leu 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-phe72ile (accessed [today's date]).

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