Is REN p.Phe130= (c.390C>T) pathogenic?

REN p.Phe130= (c.390C>T) is classified Conflicting classifications of pathogenicity in REN (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-10-28). Very rare (popmax 0.00891%, eas); Associated with familial juvenile hyperuricemic nephropathy type 2.

How common is REN p.Phe130= (c.390C>T) in the general population?

REN p.Phe130= (c.390C>T) is very rare (popmax 0.00891%, eas) (gnomAD).

REN p.Phe130=

Q: What condition is associated with REN p.Phe130= (c.390C>T)?

REN p.Phe130= (c.390C>T) is associated with familial juvenile hyperuricemic nephropathy type 2, renal tubular dysgenesis (ClinVar).

c.390C>T · rs377092171 · VCV294961

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Conditions

familial juvenile hyperuricemic nephropathy type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.29	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -5.3	GERP -1.7
Overall
CADD	9.249	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,878 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00174% 28/1,613,690 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0256%	3,906
East Asiangrpmax	0.00891%	11,220
African / African-American	0.00266%	37,524
Finnishnot grpmax-eligible	0.00156%	64,038
European (non-Finnish)	0.000424%	235,914

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe130=
Coding: c.390C>T
MANE Select: NM_001363642 · reported on NM_000537
dbSNP: rs377092171
Type: single nucleotide variant
Location: chr1:204160662 (GRCh38)
Structure: AlphaFold pLDDT 85.00

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

Disease context

familial juvenile hyperuricemic nephropathy type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: renal tubular dysgenesis

Similar variants

REN c.249+1G>A Pathogenic/Likely pathogenic ★★ same condition
REN p.Arg49Ter Pathogenic/Likely pathogenic ★★ same condition
REN p.Ala182Thr Uncertain significance ★★ ⚠ same condition
REN p.Arg119Cys Uncertain significance ★★ ⚠ same condition
REN p.Arg387Gln Uncertain significance ★★ ⚠ same condition
REN p.Arg395Trp Uncertain significance ★★ ⚠ same condition
REN p.Arg406Cys Uncertain significance ★★ ⚠ same condition
REN p.Arg43Gln Uncertain significance ★★ ⚠ same condition

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-phe130 (accessed [today's date]).

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