Is REN p.Ser296Cys (c.887C>G) pathogenic?

REN p.Ser296Cys (c.887C>G) is classified Uncertain significance in REN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-18). AlphaMissense: likely pathogenic (0.7477); Absent from gnomAD v4.1.

How common is REN p.Ser296Cys (c.887C>G) in the general population?

REN p.Ser296Cys (c.887C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about REN p.Ser296Cys (c.887C>G)?

AlphaMissense predicts likely pathogenic (score 0.7477) — an in-silico prediction, not a clinical call.

REN p.Ser296Cys

c.887C>G · rs2527481293 · VCV2728005

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7477 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7477	likely pathogenic
REVEL	0.735	pathogenic-leaning
SaProt	LLR -9.39	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Overall
CADD	27.7	PHRED · no single calibrated threshold — expert panels disagree

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.Ser296Cys
Coding: c.887C>G
MANE Select: NM_001363642 · reported on NM_000537
dbSNP: rs2527481293
Type: single nucleotide variant
Location: chr1:204156251 (GRCh38)
Structure: AlphaFold pLDDT 85.00

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

Similar variants

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
REN p.Arg387Gln 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-ser296cys (accessed [today's date]).

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