Is RNF43 p.Ala147Pro (c.439G>C) pathogenic?

RNF43 p.Ala147Pro (c.439G>C) is classified Uncertain significance in RNF43 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-20). AlphaMissense: likely pathogenic (0.9872); Absent from gnomAD v4.1.

How common is RNF43 p.Ala147Pro (c.439G>C) in the general population?

RNF43 p.Ala147Pro (c.439G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RNF43 p.Ala147Pro (c.439G>C)?

AlphaMissense predicts likely pathogenic (score 0.9872) — an in-silico prediction, not a clinical call.

RNF43 p.Ala147Pro

c.439G>C · VCV4155724

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9872 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9872	likely pathogenic · top 4% in RNF43
REVEL	0.352	indeterminate
SaProt	LLR -13.78	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 61 kb · p 1.7e-13 · regional, not allelic
Overall
CADD	30.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: RNF43
Protein: p.Ala147Pro
Coding: c.439G>C
MANE Select: NM_017763
Type: single nucleotide variant
Location: chr17:58363537 (GRCh38)
Gene constraint: LOEUF 0.632 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 55.86 · 2 PDB
Residue 147: an α-helix

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

Similar variants

RNF43 p.Ala147= Benign/Likely benign ★★ 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
RNF43 p.Ala123Thr 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-ala147pro (accessed [today's date]).

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