Is DPP3 p.Thr475Ile (c.1424C>T) pathogenic?

DPP3 p.Thr475Ile (c.1424C>T) is classified Uncertain significance in DPP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-27). AlphaMissense: likely benign (0.1125); Very rare (popmax 0.00441%, nfe).

How common is DPP3 p.Thr475Ile (c.1424C>T) in the general population?

DPP3 p.Thr475Ile (c.1424C>T) is very rare (popmax 0.00441%, nfe) (gnomAD).

What do computational predictors say about DPP3 p.Thr475Ile (c.1424C>T)?

AlphaMissense predicts likely benign (score 0.1125) — an in-silico prediction, not a clinical call.

DPP3 p.Thr475Ile

c.1424C>T · rs147328602 · VCV2474400

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1125 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00441%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1125	likely benign
REVEL	0.129	moderately benign-leaning
SaProt	LLR -11.01	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 27 kb · p 1e-05 · regional, not allelic
Overall
CADD	24.7	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 0.00441% European (non-Finnish) · 52/1,180,036 alleles

Filtering AF 0.00342% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0031%

Overall 0.00341% 55/1,612,658 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00441%	22,693
African / African-American	0.00267%	37,434
Remaining individualsnot grpmax-eligible	0.0016%	62,364

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: DPP3
Protein: p.Thr475Ile
Coding: c.1424C>T
MANE Select: NM_130443
dbSNP: rs147328602
Type: single nucleotide variant
Location: chr11:66495240 (GRCh38)
Gene constraint: LOEUF 0.827 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.56 · 10 PDB
Residue 475: a turn

Full DPP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPP3 p.Arg76His Benign ★★ ⚠ same type
DPP3 p.Leu163Met Benign ★★ ⚠ same type
DPP3 p.Lys423= Benign ★★ same type
DPP3 p.Phe331= Benign ★★ same type
DPP3 p.Phe443= Benign ★★ same type
DPP3 p.Thr401= Benign ★★ same type
DPP3 c.573+1G>A Uncertain significance ★ same type
DPP3 p.Ala22Gly 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/dpp3-p-thr475ile (accessed [today's date]).

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