Is RNF43 p.Ser607= (c.1821G>A) pathogenic?

RNF43 p.Ser607= (c.1821G>A) is classified Benign/Likely benign in RNF43 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-01). Rare (popmax 0.689%, eas); Associated with hyperplastic polyposis syndrome.

What condition is associated with RNF43 p.Ser607= (c.1821G>A)?

RNF43 p.Ser607= (c.1821G>A) is associated with hyperplastic polyposis syndrome (ClinVar).

How common is RNF43 p.Ser607= (c.1821G>A) in the general population?

RNF43 p.Ser607= (c.1821G>A) is rare (popmax 0.689%, eas) (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.Ser607=

c.1821G>A · rs200680078 · VCV1168015

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

rare (popmax 0.689%, eas)

Conditions

hyperplastic polyposis syndrome

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 -2.2	GERP -4.1
Overall
CADD	0.54	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.689% East Asian · 309/44,870 alleles

Filtering AF 0.625% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.601%

Overall 0.0608% 980/1,611,506 alleles · rare exomes 934/1,459,222 · genomes 46/152,284 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.689%	145
European (non-Finnish)	0.0517%	1,936
South Asian	0.0275%	3,630
Remaining individualsnot grpmax-eligible	0.0241%	4,154
African / African-American	0.0214%	4,681
Finnishnot grpmax-eligible	0.00626%	15,982
Admixed American	0.00336%	29,745

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.Ser607=
Coding: c.1821G>A
MANE Select: NM_017763
dbSNP: rs200680078
Type: single nucleotide variant
Location: chr17:58357955 (GRCh38)
Gene constraint: LOEUF 0.632 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 55.86 · 2 PDB
Residue 607: the 'disordered' region

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

Disease context

hyperplastic polyposis 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.Ser607Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
RNF43 p.Arg529Gln Uncertain significance ★★ ⚠ same condition
RNF43 p.Arg654Lys Uncertain significance ★★ ⚠ same condition
RNF43 p.Asp261Glu Uncertain significance ★★ ⚠ same condition
RNF43 p.Leu214Val Uncertain significance ★★ ⚠ same condition
RNF43 p.Pro569Ser Uncertain significance ★★ ⚠ same condition
RNF43 p.Pro87Leu Uncertain significance ★★ ⚠ same condition
RNF43 p.Ser227Asn 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-ser607 (accessed [today's date]).

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