Is DPEP2 p.Glu151Lys (c.451G>A) pathogenic?

DPEP2 p.Glu151Lys (c.451G>A) is classified Uncertain significance in DPEP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-22). AlphaMissense: ambiguous (0.4837); Very rare (popmax 0.00475%, nfe).

How common is DPEP2 p.Glu151Lys (c.451G>A) in the general population?

DPEP2 p.Glu151Lys (c.451G>A) is very rare (popmax 0.00475%, nfe) (gnomAD).

What do computational predictors say about DPEP2 p.Glu151Lys (c.451G>A)?

AlphaMissense predicts ambiguous (score 0.4837) — an in-silico prediction, not a clinical call.

DPEP2 p.Glu151Lys

c.451G>A · VCV4244364

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4837 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00475%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4837	ambiguous
REVEL	0.467	indeterminate
SaProt	LLR -13.16	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 5,703 bp · p 0.27 · regional, not allelic
Overall
CADD	27.8	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 0.00475% European (non-Finnish) · 56/1,180,038 alleles

Filtering AF 0.00375% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00337%

Overall 0.00366% 59/1,614,062 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00475%	21,072
African / African-American	0.00267%	37,460
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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.Glu151Lys
Coding: c.451G>A
MANE Select: NM_022355
Type: single nucleotide variant
Location: chr16:67992133 (GRCh38)
Gene constraint: LOEUF 1.089 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.94
Residue 151: a disulfide bond

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

Similar variants

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
DPEP2 p.Arg158Cys 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-glu151lys (accessed [today's date]).

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