Is RNF43 p.Pro112Ser (c.334C>T) pathogenic?

RNF43 p.Pro112Ser (c.334C>T) is classified Uncertain significance in RNF43 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-19). AlphaMissense: ambiguous (0.5473); Absent from gnomAD v4.1.

How common is RNF43 p.Pro112Ser (c.334C>T) in the general population?

RNF43 p.Pro112Ser (c.334C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RNF43 p.Pro112Ser (c.334C>T)?

AlphaMissense predicts ambiguous (score 0.5473) — an in-silico prediction, not a clinical call.

RNF43 p.Pro112Ser

c.334C>T · rs2143514724 · VCV2819983

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5473 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5473	ambiguous
REVEL	0.263	benign-leaning
SaProt	LLR -9.48	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 61 kb · p 1.7e-13 · regional, not allelic
Overall
CADD	24.8	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: RNF43
Protein: p.Pro112Ser
Coding: c.334C>T
MANE Select: NM_017763
dbSNP: rs2143514724
Type: single nucleotide variant
Location: chr17:58370952 (GRCh38)
Gene constraint: LOEUF 0.632 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 55.86 · 2 PDB
Residue 112: a turn

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

Similar variants

RNF43 p.Pro112= 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-pro112ser (accessed [today's date]).

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