Is RNF213 p.Ala4530Val (c.13589C>T) pathogenic?

RNF213 p.Ala4530Val (c.13589C>T) is classified Likely benign in RNF213 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-23). AlphaMissense: likely benign (0.0775); Ultra-rare (popmax 0.0491%, nfe).

How common is RNF213 p.Ala4530Val (c.13589C>T) in the general population?

RNF213 p.Ala4530Val (c.13589C>T) is ultra-rare (popmax 0.0491%, nfe) (gnomAD).

What do computational predictors say about RNF213 p.Ala4530Val (c.13589C>T)?

AlphaMissense predicts likely benign (score 0.0775) — an in-silico prediction, not a clinical call.

RNF213 p.Ala4530Val

c.13589C>T · rs151100315 · VCV968995

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0775 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0491%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0775	likely benign
REVEL	0.098	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.8	GERP 0.52
Regional constraint	o/e 0.93	unconstrained · MANE · 24 kb · p 0.01 · regional, not allelic
Overall
CADD	4.721	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0491% European (non-Finnish) · 579/1,180,032 alleles

Filtering AF 0.0458% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0444%

Overall 0.0376% 607/1,614,188 alleles · ultra-rare exomes 587/1,461,872 · genomes 20/152,316 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0491%	2,038
African / African-American	0.02%	5,004
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0112%	8,930
East Asian	0.00668%	14,961
Finnishnot grpmax-eligible	0.00156%	64,024
South Asian	0.0011%	91,080

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.Ala4530Val
Coding: c.13589C>T
MANE Select: NM_001256071
dbSNP: rs151100315
Type: single nucleotide variant
Location: chr17:80379663 (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.Ala4530= Benign/Likely benign ★★ same residue
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

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-ala4530val (accessed [today's date]).

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