Is RNF213 p.Pro2873= (c.8619C>T) pathogenic?

RNF213 p.Pro2873= (c.8619C>T) is classified Benign in RNF213 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-07). Rare (popmax 0.22%, amr).

How common is RNF213 p.Pro2873= (c.8619C>T) in the general population?

RNF213 p.Pro2873= (c.8619C>T) is rare (popmax 0.22%, amr) (gnomAD).

RNF213 p.Pro2873=

c.8619C>T · VCV4809152

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.22%, amr)

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 -8.2	GERP -3.8
Overall
CADD	0.116	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.22% Admixed American · 132/59,958 alleles

Filtering AF 0.19% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.178%

Overall 0.0138% 223/1,613,694 alleles · rare exomes 201/1,461,558 · genomes 22/152,136 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.22%	454
South Asian	0.0428%	2,335
Middle Eastern	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.0128%	7,807
African / African-American	0.00534%	18,726
Finnishnot grpmax-eligible	0.00469%	21,331
European (non-Finnish)	0.00297%	33,711
East Asian	0.00223%	44,870

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: RNF213
Protein: p.Pro2873=
Coding: c.8619C>T
MANE Select: NM_001256071
Type: single nucleotide variant
Location: chr17:80346954 (GRCh38)
Gene constraint: LOEUF 0.692 · pLI <0.01 (gnomAD)

Full RNF213 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RNF213 p.Ala5114Thr Uncertain significance ★★ ⚠ same type
RNF213 p.Arg2727Gly Uncertain significance ★★ ⚠ same type
RNF213 p.Arg3585His Uncertain significance ★★ ⚠ same type
RNF213 p.Arg4276Trp Uncertain significance ★★ ⚠ same type
RNF213 p.Arg4492Gln Uncertain significance ★★ ⚠ same type
RNF213 p.Arg4810Ser Uncertain significance ★★ ⚠ same type
RNF213 p.Arg4958Trp Uncertain significance ★★ ⚠ same type
RNF213 p.Asn1439Ser 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/rnf213-p-pro2873 (accessed [today's date]).

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