Is REN p.Phe210= (c.630C>T) pathogenic?

REN p.Phe210= (c.630C>T) is classified Conflicting classifications of pathogenicity in REN (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-06-12). Ultra-rare (popmax 0.088%, afr); Associated with familial juvenile hyperuricemic nephropathy type 2.

How common is REN p.Phe210= (c.630C>T) in the general population?

REN p.Phe210= (c.630C>T) is ultra-rare (popmax 0.088%, afr) (gnomAD).

REN p.Phe210=

Q: What condition is associated with REN p.Phe210= (c.630C>T)?

REN p.Phe210= (c.630C>T) is associated with familial juvenile hyperuricemic nephropathy type 2, renal tubular dysgenesis (ClinVar).

c.630C>T · rs141706094 · VCV294957

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.088%, afr)

Conditions

familial juvenile hyperuricemic nephropathy type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.66	GERP -2.1, phastCons 0.92
Overall
CADD	8.057	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.088% African / African-American · 66/74,992 alleles

Filtering AF 0.0709% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0647%

Overall 0.0424% 684/1,614,072 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.088%	1,136
European (non-Finnish)	0.0503%	1,990
Remaining individualsnot grpmax-eligible	0.0176%	5,682
South Asian	0.00878%	11,385
Admixed American	0.00833%	12,003
East Asian	0.00223%	44,868

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.Phe210=
Coding: c.630C>T
MANE Select: NM_001363642 · reported on NM_000537
dbSNP: rs141706094
Type: single nucleotide variant
Location: chr1:204159458 (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-phe210 (accessed [today's date]).

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