Is RNF43 p.Arg219= (c.657C>T) pathogenic?

RNF43 p.Arg219= (c.657C>T) is classified Benign in RNF43 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-06-30). Absent from gnomAD v4.1; Associated with sessile serrated polyposis cancer syndrome.

What condition is associated with RNF43 p.Arg219= (c.657C>T)?

RNF43 p.Arg219= (c.657C>T) is associated with sessile serrated polyposis cancer syndrome (ClinVar).

How common is RNF43 p.Arg219= (c.657C>T) in the general population?

RNF43 p.Arg219= (c.657C>T) is absent from gnomAD v4.1 (gnomAD).

How is Serrated polyposis syndrome inherited?

Typically Autosomal dominant, Multigenic/multifactorial (Orphanet). A genetic counselor can assess individual risk for a family.

RNF43 p.Arg219=

c.657C>T · VCV4875773

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

sessile serrated polyposis cancer syndrome

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 -0.7	GERP -4.2
Overall
CADD	5.232	PHRED · no single calibrated threshold — expert panels disagree

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: RNF43
Protein: p.Arg219=
Coding: c.657C>T
MANE Select: NM_017763
Type: single nucleotide variant
Location: chr17:58362574 (GRCh38)
Gene constraint: LOEUF 0.632 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 55.86 · 2 PDB

Full RNF43 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

sessile serrated polyposis cancer syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Serrated polyposis syndrome (Orphanet):

Inheritance: Autosomal dominant, Multigenic/multifactorial, Unknown
Onset: Adult, Elderly
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

RNF43 p.Arg219Cys Uncertain significance ★★ ⚠ same residue
RNF43 p.Arg219His Uncertain significance ★★ ⚠ same residue
RNF43 p.Arg219Leu Uncertain significance ★ same residue
RNF43 p.Arg337Ter Pathogenic/Likely pathogenic ★★ same condition
RNF43 c.688-3C>T Uncertain significance ★★ same condition
RNF43 p.Ala115Val Uncertain significance ★★ ⚠ same condition
RNF43 p.Ala126Val Uncertain significance ★★ ⚠ same condition
RNF43 p.Ala148Gly 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/rnf43-p-arg219 (accessed [today's date]).

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