Is DPP3 p.Glu291Lys (c.871G>A) pathogenic?

DPP3 p.Glu291Lys (c.871G>A) is classified Uncertain significance in DPP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-29). AlphaMissense: likely benign (0.1297); Very rare (popmax 0.00223%, eas).

How common is DPP3 p.Glu291Lys (c.871G>A) in the general population?

DPP3 p.Glu291Lys (c.871G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about DPP3 p.Glu291Lys (c.871G>A)?

AlphaMissense predicts likely benign (score 0.1297) — an in-silico prediction, not a clinical call.

DPP3 p.Glu291Lys

c.871G>A · rs368941305 · VCV2607428

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1297 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1297	likely benign
REVEL	0.157	moderately benign-leaning
SaProt	LLR -12.56	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 8.4	GERP 2.2, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 27 kb · p 1e-05 · regional, not allelic
Overall
CADD	23.2	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 0.00223% East Asian · 1/44,878 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000496% 8/1,613,714 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,878
African / African-American	0.00134%	74,888
South Asian	0.0011%	91,054
European (non-Finnish)	0.000424%	235,977

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.Glu291Lys
Coding: c.871G>A
MANE Select: NM_130443
dbSNP: rs368941305
Type: single nucleotide variant
Location: chr11:66491566 (GRCh38)
Gene constraint: LOEUF 0.827 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.56 · 10 PDB
Residue 291: 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.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-glu291lys (accessed [today's date]).

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