Is REN p.Arg43Gln (c.128G>A) pathogenic?

REN p.Arg43Gln (c.128G>A) is classified Uncertain significance in REN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-01). AlphaMissense: likely benign (0.1879); Very rare (popmax 0.0011%, sas); Associated with renal tubular dysgenesis of genetic origin.

What condition is associated with REN p.Arg43Gln (c.128G>A)?

REN p.Arg43Gln (c.128G>A) is associated with renal tubular dysgenesis of genetic origin, familial juvenile hyperuricemic nephropathy type 2 (ClinVar).

How common is REN p.Arg43Gln (c.128G>A) in the general population?

REN p.Arg43Gln (c.128G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about REN p.Arg43Gln (c.128G>A)?

AlphaMissense predicts likely benign (score 0.1879) — an in-silico prediction, not a clinical call.

REN p.Arg43Gln

c.128G>A · VCV3578131

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1879 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

renal tubular dysgenesis of genetic origin

Computational evidence

Protein change
AlphaMissense	0.1879	likely benign
REVEL	0.518	indeterminate
SaProt	LLR -7.11	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.61 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.08	GERP 0.36
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,072 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.000752% 11/1,461,854 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,072
European (non-Finnish)	0.000847%	118,001

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.Arg43Gln
Coding: c.128G>A
MANE Select: NM_001363642 · reported on NM_000537
Type: single nucleotide variant
Location: chr1:204162134 (GRCh38)
Structure: AlphaFold pLDDT 85.00
Residue 43: the btb domain

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

Disease context

renal tubular dysgenesis of genetic origin — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial juvenile hyperuricemic nephropathy type 2

Similar variants

REN p.Arg43Ter Pathogenic ★ same residue
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

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-arg43gln (accessed [today's date]).

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