Is REN p.Arg387Ter (c.1159C>T) pathogenic?

REN p.Arg387Ter (c.1159C>T) is classified Pathogenic in REN (ClinVar, No assertion criteria, 1 submitter; last evaluated 1994-12-02). Very rare (popmax 0.000424%, nfe); Associated with HYPERPRORENINEMIA, FAMILIAL.

What condition is associated with REN p.Arg387Ter (c.1159C>T)?

REN p.Arg387Ter (c.1159C>T) is associated with HYPERPRORENINEMIA, FAMILIAL (ClinVar).

How common is REN p.Arg387Ter (c.1159C>T) in the general population?

REN p.Arg387Ter (c.1159C>T) is very rare (popmax 0.000424%, nfe) (gnomAD).

REN p.Arg387Ter

c.1159C>T · rs121917740 · VCV13122

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Conditions

HYPERPRORENINEMIA, FAMILIAL

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP -0.071, phastCons 1
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,180,006 alleles

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

Overall 0.000342% 5/1,461,882 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: REN
Protein: p.Arg387Ter
Coding: c.1159C>T
MANE Select: NM_001363642 · reported on NM_000537
dbSNP: rs121917740
Type: single nucleotide variant
Location: chr1:204155078 (GRCh38)
Structure: AlphaFold pLDDT 85.00

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

Disease context

HYPERPRORENINEMIA, FAMILIAL — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

REN p.Arg387Gln Uncertain significance ★★ ⚠ same residue
REN c.249+1G>A Pathogenic/Likely pathogenic ★★ same type
REN p.Arg49Ter Pathogenic/Likely pathogenic ★★ same type
REN p.Lys139Ter Pathogenic ★★ same type
REN p.Ala182Thr Uncertain significance ★★ ⚠ same type
REN p.Arg119Cys Uncertain significance ★★ ⚠ same type
REN p.Arg119His Uncertain significance ★★ ⚠ same type
REN p.Arg148His 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/ren-p-arg387ter (accessed [today's date]).

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