Is DPEP1 p.Pro173Arg (c.518C>G) pathogenic?

DPEP1 p.Pro173Arg (c.518C>G) is classified Uncertain significance in DPEP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-01). AlphaMissense: ambiguous (0.5068); Very rare (popmax 0.00415%, nfe).

How common is DPEP1 p.Pro173Arg (c.518C>G) in the general population?

DPEP1 p.Pro173Arg (c.518C>G) is very rare (popmax 0.00415%, nfe) (gnomAD).

What do computational predictors say about DPEP1 p.Pro173Arg (c.518C>G)?

AlphaMissense predicts ambiguous (score 0.5068) — an in-silico prediction, not a clinical call.

DPEP1 p.Pro173Arg

c.518C>G · VCV4014509

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5068 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00415%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5068	ambiguous
REVEL	0.463	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 1.20	unconstrained · MANE · 7,808 bp · p 2.9e-06 · regional, not allelic
Overall
CADD	27.1	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 0.00415% European (non-Finnish) · 49/1,179,890 alleles

Filtering AF 0.00318% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00286%

Overall 0.00304% 49/1,612,210 alleles · very rare

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: DPEP1
Protein: p.Pro173Arg
Coding: c.518C>G
MANE Select: NM_001389466
Type: single nucleotide variant
Location: chr16:89636680 (GRCh38)
Gene constraint: LOEUF 1.505 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.34 · 2 PDB
Residue 173: a β-strand

Full DPEP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPEP1 p.Ala155Glu Uncertain significance ★ ⚠ same type
DPEP1 p.Ala155Thr Uncertain significance ★ ⚠ same type
DPEP1 p.Ala296Val Uncertain significance ★ ⚠ same type
DPEP1 p.Ala326Thr Uncertain significance ★ ⚠ same type
DPEP1 p.Ala402Asp Uncertain significance ★ ⚠ same type
DPEP1 p.Arg107Leu Uncertain significance ★ ⚠ same type
DPEP1 p.Arg110Trp Uncertain significance ★ ⚠ same type
DPEP1 p.Arg126Gln 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/dpep1-p-pro173arg (accessed [today's date]).

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