Is RNF43 p.Pro587= (c.1761C>T) pathogenic?

RNF43 p.Pro587= (c.1761C>T) is classified Likely benign in RNF43 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-15). Very rare (popmax 0.00341%, nfe).

How common is RNF43 p.Pro587= (c.1761C>T) in the general population?

RNF43 p.Pro587= (c.1761C>T) is very rare (popmax 0.00341%, nfe) (gnomAD).

RNF43 p.Pro587=

c.1761C>T · rs750381274 · VCV1110635

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00341%, nfe)

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 0.3	GERP -4.1, phastCons 0.03
Overall
CADD	5.298	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00341% European (non-Finnish) · 40/1,172,078 alleles

Filtering AF 0.00257% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00226%

Overall 0.00263% 42/1,596,502 alleles · very rare exomes 41/1,444,334 · genomes 1/152,168 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00341%	29,302
Remaining individualsnot grpmax-eligible	0.00325%	30,775

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: RNF43
Protein: p.Pro587=
Coding: c.1761C>T
MANE Select: NM_017763
dbSNP: rs750381274
Type: single nucleotide variant
Location: chr17:58358015 (GRCh38)
Gene constraint: LOEUF 0.632 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 55.86 · 2 PDB
Residue 587: the 'disordered' region

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

Similar variants

RNF43 p.Pro587Ala Uncertain significance ★ ⚠ same residue
RNF43 p.Pro587Leu Conflicting classifications of pathogenicity ★ ⚠ 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
RNF43 p.Ala115Val 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-pro587 (accessed [today's date]).

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