Is REN p.Ser278Pro (c.832T>C) pathogenic?

REN p.Ser278Pro (c.832T>C) is classified Uncertain significance in REN (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). AlphaMissense: likely benign (0.0867); Absent from gnomAD v4.1; Associated with renal tubular dysgenesis.

What condition is associated with REN p.Ser278Pro (c.832T>C)?

REN p.Ser278Pro (c.832T>C) is associated with renal tubular dysgenesis, familial juvenile hyperuricemic nephropathy type 2 (ClinVar).

How common is REN p.Ser278Pro (c.832T>C) in the general population?

REN p.Ser278Pro (c.832T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about REN p.Ser278Pro (c.832T>C)?

AlphaMissense predicts likely benign (score 0.0867) — an in-silico prediction, not a clinical call.

REN p.Ser278Pro

c.832T>C · rs1658148781 · VCV873769

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0867 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

renal tubular dysgenesis

Computational evidence

Protein change
AlphaMissense	0.0867	likely benign
REVEL	0.103	moderately benign-leaning
SaProt	LLR -9.20	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP -0.27, phastCons 1
Overall
CADD	22.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: REN
Protein: p.Ser278Pro
Coding: c.832T>C
MANE Select: NM_001363642 · reported on NM_000537
dbSNP: rs1658148781
Type: single nucleotide variant
Location: chr1:204156306 (GRCh38)
Structure: AlphaFold pLDDT 85.00

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

Disease context

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

Also linked: familial juvenile hyperuricemic nephropathy type 2

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-ser278pro (accessed [today's date]).

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