Is DPP4 p.Thr94Ile (c.281C>T) pathogenic?

DPP4 p.Thr94Ile (c.281C>T) is classified Uncertain significance in DPP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). AlphaMissense: likely benign (0.2826); Very rare (popmax 0.00836%, amr).

How common is DPP4 p.Thr94Ile (c.281C>T) in the general population?

DPP4 p.Thr94Ile (c.281C>T) is very rare (popmax 0.00836%, amr) (gnomAD).

What do computational predictors say about DPP4 p.Thr94Ile (c.281C>T)?

AlphaMissense predicts likely benign (score 0.2826) — an in-silico prediction, not a clinical call.

DPP4 p.Thr94Ile

c.281C>T · rs750539982 · VCV2269987

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2826 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00836%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2826	likely benign
REVEL	0.704	pathogenic-leaning
SaProt	LLR -8.81	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 2.5, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 81 kb · p 0.82 · regional, not allelic
Overall
CADD	23.0	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 0.00836% Admixed American · 5/59,828 alleles

Filtering AF 0.00324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.0014% 22/1,566,500 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00836%	11,966
Ashkenazi Jewishnot grpmax-eligible	0.00682%	14,659
Remaining individualsnot grpmax-eligible	0.00328%	30,459
African / African-American	0.00271%	36,953
East Asian	0.00224%	44,624
South Asian	0.00222%	44,950
European (non-Finnish)	0.000703%	142,147

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: DPP4
Protein: p.Thr94Ile
Coding: c.281C>T
MANE Select: NM_001935
dbSNP: rs750539982
Type: single nucleotide variant
Location: chr2:162046919 (GRCh38)
Gene constraint: LOEUF 0.901 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.45 · 121 PDB
Residue 94: a turn

Full DPP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPP4 c.1987+4T>C Benign ★★ same type
DPP4 p.Ala16= Benign ★★ same type
DPP4 p.Gly645= Benign ★★ same type
DPP4 p.Leu27= Benign ★★ same type
DPP4 p.Lys539= Likely benign ★★ same type
DPP4 p.Ser437Thr Benign ★★ ⚠ same type
DPP4 p.Val266Ile Likely benign ★★ ⚠ same type
DPP4 p.Ala654Thr 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/dpp4-p-thr94ile (accessed [today's date]).

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