Is RNF43 p.Pro669= (c.2007C>T) pathogenic?

RNF43 p.Pro669= (c.2007C>T) is classified Likely benign in RNF43 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-08). Absent from gnomAD v4.1.

How common is RNF43 p.Pro669= (c.2007C>T) in the general population?

RNF43 p.Pro669= (c.2007C>T) is absent from gnomAD v4.1 (gnomAD).

RNF43 p.Pro669=

c.2007C>T · rs2143393164 · VCV2165324

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3	GERP -1.2, phastCons 1
Overall
CADD	5.003	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.Pro669=
Coding: c.2007C>T
MANE Select: NM_017763
dbSNP: rs2143393164
Type: single nucleotide variant
Location: chr17:58357769 (GRCh38)
Gene constraint: LOEUF 0.632 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 55.86 · 2 PDB
Residue 669: the 'disordered' region

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

Similar variants

RNF43 p.Pro669Leu Uncertain significance ★★ ⚠ same residue
RNF43 p.Pro669Ser Uncertain significance ★★ ⚠ same residue
RNF43 p.Pro669His Uncertain significance ★ ⚠ same residue
RNF43 p.Arg337Ter Pathogenic/Likely pathogenic ★★ same type
RNF43 c.252+2C>G Uncertain significance ★★ same type
RNF43 c.687+5G>T Uncertain significance ★★ same type
RNF43 c.688-3C>T Uncertain significance ★★ same type
RNF43 p.Ala115Asp 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/rnf43-p-pro669 (accessed [today's date]).

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