Is DPEP2 p.Pro39Ser (c.115C>T) pathogenic?

DPEP2 p.Pro39Ser (c.115C>T) is classified Uncertain significance in DPEP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-12). AlphaMissense: likely benign (0.0595); Ultra-rare (popmax 0.0169%, mid).

How common is DPEP2 p.Pro39Ser (c.115C>T) in the general population?

DPEP2 p.Pro39Ser (c.115C>T) is ultra-rare (popmax 0.0169%, mid) (gnomAD).

What do computational predictors say about DPEP2 p.Pro39Ser (c.115C>T)?

AlphaMissense predicts likely benign (score 0.0595) — an in-silico prediction, not a clinical call.

DPEP2 p.Pro39Ser

c.115C>T · VCV4661896

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0595 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0169%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0595	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -6.06	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.4	GERP -2.7
Regional constraint	o/e 0.96	unconstrained · MANE · 5,703 bp · p 0.27 · regional, not allelic
Overall
CADD	0.002	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0169% Middle Eastern · 1/5,916 alleles

Overall 0.000212% 3/1,414,912 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0169%	5,916
Ashkenazi Jewishnot grpmax-eligible	0.0035%	28,532
European (non-Finnish)	8.66e-05%	1,155,151

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: DPEP2
Protein: p.Pro39Ser
Coding: c.115C>T
MANE Select: NM_022355
Type: single nucleotide variant
Location: chr16:67993098 (GRCh38)
Gene constraint: LOEUF 1.089 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.94

Full DPEP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPEP2 p.Pro39Leu Uncertain significance ★ ⚠ same residue
DPEP2 p.Ala226Thr Uncertain significance ★ ⚠ same type
DPEP2 p.Ala276Thr Uncertain significance ★ ⚠ same type
DPEP2 p.Ala33Thr Uncertain significance ★ ⚠ same type
DPEP2 p.Ala59Thr Uncertain significance ★ ⚠ same type
DPEP2 p.Ala78Val Uncertain significance ★ ⚠ same type
DPEP2 p.Arg147Cys Uncertain significance ★ ⚠ same type
DPEP2 p.Arg147His 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/dpep2-p-pro39ser (accessed [today's date]).

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