Is DPP7 p.Thr304Met (c.911C>T) pathogenic?

DPP7 p.Thr304Met (c.911C>T) is classified Uncertain significance in DPP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-28). AlphaMissense: likely benign (0.1384); Ultra-rare (popmax 0.0363%, nfe).

How common is DPP7 p.Thr304Met (c.911C>T) in the general population?

DPP7 p.Thr304Met (c.911C>T) is ultra-rare (popmax 0.0363%, nfe) (gnomAD).

What do computational predictors say about DPP7 p.Thr304Met (c.911C>T)?

AlphaMissense predicts likely benign (score 0.1384) — an in-silico prediction, not a clinical call.

DPP7 p.Thr304Met

c.911C>T · rs139554508 · VCV2372598

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1384 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0363%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1384	likely benign
REVEL	0.265	benign-leaning
SaProt	LLR -8.61	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.36 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2.7	GERP -2.6
Regional constraint	o/e 1.17	unconstrained · MANE · 3,355 bp · p 5.6e-05 · regional, not allelic
Overall
CADD	0.177	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 0.0363% European (non-Finnish) · 428/1,179,062 alleles

Filtering AF 0.0334% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0323%

Overall 0.0294% 473/1,608,198 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0363%	2,755
Remaining individualsnot grpmax-eligible	0.0273%	3,664
African / African-American	0.02%	5,002
Middle Eastern	0.0167%	5,974
Admixed American	0.0151%	6,636
East Asian	0.00223%	44,758
Finnishnot grpmax-eligible	0.00166%	60,384
South Asian	0.0011%	90,568

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.Thr304Met
Coding: c.911C>T
MANE Select: NM_013379
dbSNP: rs139554508
Type: single nucleotide variant
Location: chr9:137112765 (GRCh38)
Gene constraint: LOEUF 1.707 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.44 · 3 PDB
Residue 304: 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-thr304met (accessed [today's date]).

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