Is DPP4 p.Tyr372Cys (c.1115A>G) pathogenic?

DPP4 p.Tyr372Cys (c.1115A>G) is classified Uncertain significance in DPP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-08). AlphaMissense: ambiguous (0.3735); Very rare (popmax 0.00668%, afr).

How common is DPP4 p.Tyr372Cys (c.1115A>G) in the general population?

DPP4 p.Tyr372Cys (c.1115A>G) is very rare (popmax 0.00668%, afr) (gnomAD).

What do computational predictors say about DPP4 p.Tyr372Cys (c.1115A>G)?

AlphaMissense predicts ambiguous (score 0.3735) — an in-silico prediction, not a clinical call.

DPP4 p.Tyr372Cys

c.1115A>G · VCV4014616

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3735 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3735	ambiguous
REVEL	0.939	strongly pathogenic-leaning
SaProt	LLR -14.16	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.5, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 81 kb · p 0.82 · regional, not allelic
Overall
CADD	26.8	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 0.00668% African / African-American · 5/74,872 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.000372% 6/1,612,860 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00668%	14,974
South Asian	0.0011%	90,608

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.Tyr372Cys
Coding: c.1115A>G
MANE Select: NM_001935
Type: single nucleotide variant
Location: chr2:162020642 (GRCh38)
Gene constraint: LOEUF 0.901 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.45 · 121 PDB
Residue 372: a β-strand

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-tyr372cys (accessed [today's date]).

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