Is ECPAS p.Pro1390Arg (c.4169C>G) pathogenic?

ECPAS p.Pro1390Arg (c.4169C>G) is classified Uncertain significance in ECPAS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-25). Very rare (popmax 6.85e-05%).

How common is ECPAS p.Pro1390Arg (c.4169C>G) in the general population?

ECPAS p.Pro1390Arg (c.4169C>G) is very rare (popmax 6.85e-05%) (gnomAD).

ECPAS p.Pro1390Arg

c.4169C>G · VCV3506554

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.85e-05%)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.745	pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 48 kb · p 1.8e-10 · regional, not allelic
Overall
CADD	28.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.85e-05%

Overall 6.85e-05% 1/1,459,652 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: ECPAS
Protein: p.Pro1390Arg
Coding: c.4169C>G
MANE Select: NM_001364929
Type: single nucleotide variant
Location: chr9:111373980 (GRCh38)
Gene constraint: LOEUF 0.316 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.03

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

Similar variants

ECPAS c.270+1G>T Uncertain significance ★ same type
ECPAS c.-128G>A Uncertain significance ★ same type
ECPAS c.-128G>C Uncertain significance ★ same type
ECPAS c.-138C>T Uncertain significance ★ same type
ECPAS c.-150C>T Uncertain significance ★ same type
ECPAS c.-152C>T Uncertain significance ★ same type
ECPAS c.-176C>G Uncertain significance ★ same type
ECPAS c.-186C>T 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/ecpas-p-pro1390arg (accessed [today's date]).

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