Is DPP7 p.Thr75Ala (c.223A>G) pathogenic?

DPP7 p.Thr75Ala (c.223A>G) is classified Uncertain significance in DPP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-09). AlphaMissense: likely benign (0.1245); Very rare (popmax 0.00167%, amr).

How common is DPP7 p.Thr75Ala (c.223A>G) in the general population?

DPP7 p.Thr75Ala (c.223A>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DPP7 p.Thr75Ala (c.223A>G)?

AlphaMissense predicts likely benign (score 0.1245) — an in-silico prediction, not a clinical call.

DPP7 p.Thr75Ala

c.223A>G · VCV3504973

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1245 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1245	likely benign
REVEL	0.345	indeterminate
SaProt	LLR -8.30	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP 1.2, phastCons 1
Regional constraint	o/e 1.35	unconstrained · MANE · 416 bp · p 8.2e-05 · regional, not allelic
Overall
CADD	23.3	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 0.00167% Admixed American · 1/59,814 alleles

Overall 6.88e-05% 1/1,454,304 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.Thr75Ala
Coding: c.223A>G
MANE Select: NM_013379
Type: single nucleotide variant
Location: chr9:137114341 (GRCh38)
Gene constraint: LOEUF 1.707 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.44 · 3 PDB
Residue 75: a β-strand

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-thr75ala (accessed [today's date]).

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