Is RNF213 p.Thr808Met (c.2423C>T) pathogenic?

RNF213 p.Thr808Met (c.2423C>T) is classified Benign in RNF213 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-25). AlphaMissense: likely benign (0.0829); Low-frequency (popmax 3.51%, afr).

How common is RNF213 p.Thr808Met (c.2423C>T) in the general population?

RNF213 p.Thr808Met (c.2423C>T) is low-frequency (popmax 3.51%, afr) (gnomAD).

What do computational predictors say about RNF213 p.Thr808Met (c.2423C>T)?

AlphaMissense predicts likely benign (score 0.0829) — an in-silico prediction, not a clinical call.

RNF213 p.Thr808Met

c.2423C>T · rs74455936 · VCV775390

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0829 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.51%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0829	likely benign
REVEL	0.009	strongly benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP -8.3	GERP -3.5
Regional constraint	o/e 0.88	unconstrained · MANE · 27 kb · p 0.0016 · regional, not allelic
Overall
CADD	0.001	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 3.51% African / African-American · 2,633/74,964 alleles

Filtering AF 3.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.36%

Overall 0.208% 3,357/1,613,802 alleles · low-frequency exomes 1,798/1,461,646 · genomes 1,559/152,156 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.51%	28
Ashkenazi Jewishnot grpmax-eligible	0.422%	237
Middle Eastern	0.348%	287
Remaining individualsnot grpmax-eligible	0.29%	345
Admixed American	0.287%	349
European (non-Finnish)	0.0186%	5,363
South Asian	0.00549%	18,213

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.Thr808Met
Coding: c.2423C>T
MANE Select: NM_001256071
dbSNP: rs74455936
Type: single nucleotide variant
Location: chr17:80306464 (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.Thr808= 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-thr808met (accessed [today's date]).

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