Is DPP3 p.Phe443= (c.1329C>T) pathogenic?

DPP3 p.Phe443= (c.1329C>T) is classified Benign in DPP3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-05-21). Common (popmax 7.75%, afr) — too common for a highly-penetrant pathogenic allele.

DPP3 p.Phe443=

Q: How common is DPP3 p.Phe443= (c.1329C>T) in the general population?

DPP3 p.Phe443= (c.1329C>T) is common (popmax 7.75%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1329C>T · rs76777675 · VCV784195

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 7.75%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.8	GERP -4.7
Overall
CADD	7.15	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.75% African / African-American · 5,813/75,010 alleles

Filtering AF 7.58% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.52%

Overall 0.411% 6,627/1,613,164 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.75%	13
Remaining individualsnot grpmax-eligible	0.544%	184
Admixed American	0.513%	195
Middle Eastern	0.232%	432
South Asian	0.022%	4,553
European (non-Finnish)	0.0112%	8,939

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.Phe443=
Coding: c.1329C>T
MANE Select: NM_130443
dbSNP: rs76777675
Type: single nucleotide variant
Location: chr11:66493573 (GRCh38)
Gene constraint: LOEUF 0.827 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.56 · 10 PDB
Residue 443: an α-helix

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.Thr401= Benign ★★ same type
DPP3 c.573+1G>A Uncertain significance ★ same type
DPP3 p.Ala22Gly Uncertain significance ★ ⚠ same type
DPP3 p.Ala22Thr 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-phe443 (accessed [today's date]).

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